1. health and fitness
2. disease

CM E
Vitiligo: Treatment Approach in Children
Arin L. Isenstein, MD; Dean S. Morrell, MD; and Craig N. Burkhart, MD
CM E
EDUCATIONAL OBJECTIVES
1. Describe the psychosocial impact of
vitiligo in the pediatric population.
2. Identify current treatment options
for pediatric vitiligo.
3. Explain the indications for referral of a
child with vitiligo to a dermatologist.
Arin L. Isenstein, MD, is Resident Physician, Department of Dermatology, University of North Carolina; Dean S. Morrell,
MD, is Associate Professor, Department
of Dermatology, University of North Carolina; Craig N. Burkhart, MD, is Assistant
Professor, Department of Dermatology,
University of North Carolina.
Address correspondence to: UNC Dermatology, 3100 Thurston-Bowles Bldg.,
CB#7287, Chapel Hill, NC, 27599-7287;
fax 919-966-3898; e-mail aisenste@
unch.unc.edu.
Dr. Isenstein, Dr. Morrell, and Dr.
Burkhart have disclosed no relevant financial relationships.
doi: 10.3928/00904481-20090522-01
V
itiligo is a common acquired condition in which the skin and hair
become depigmented or hypopigmented. The prevalence of vitiligo ranges
between 0.5% and 2% worldwide, and
50% of the cases present before 20 years.1,2
Given the visibility of the disease, vitiligo
can have psychological effects including
low self-esteem, teasing by others, and
social anxiety. Topical therapies and pho-
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3806Isenstein.indd 339
Figure 1. Acrally distributed vitiligo in areas of trauma. Photos courtesy Dean Morrell, MD.
totherapy can safely and effectively repigment the skin and improve quality of life.
Here we provide a review of the clinical
presentation, epidemiology, associations,
pathogenesis, and treatment of vitiligo in
the pediatric population.
CLINICAL PRESENTATION
Vitiligo presents as acquired depigmented or hypopigmented macules of
various geographic patterns. It is nonpalpable, not scaly, and asymptomatic.
In classic cases, the diagnosis can be
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TABLE 1.
Subtypes of Vitiligo in Pediatric Patients
Subtypes of Vitiligo
Percentage of Cases
Generalized (vitiligo vulgaris)
33-78
Focal
14-29
Segmental
4-19
Acrofacial
1-10
Universal
Rare
TABLE 2.
Differential Diagnosis
of Vitiligo in a Pediatric
Population
Tinea versicolor
Pityriasis alba
Postinflammatory hypopigmentation
Lichen sclerosus
Nevus depigmentosus
Nevus anemicus
Tuberous sclerosis
Piebaldism
made in the primary care setting.3 Often
sites of trauma are favored as demonstrated by frequent involvement on the
hands, elbows and knees (see Figure 1,
page 339). Vitiligo is classified into subtypes based on the pattern and extent of
involvement (see Table 1). Generalized
vitiligo, also known as vitiligo vulgaris,
is the most common type of vitiligo in
pediatric patients, ranging from 33% to
78%.2,4-6 These patients have scattered
depigmented macules in a symmetric
fashion on the face, neck, torso, extensor aspects of extremities, and over bony
prominences (Figure 2, see page 341).
Focal vitiligo is seen in 14% to 29% of
pediatric patients with vitiligo and is defined as localized depigmented macules
in a non-dermatomal pattern.2,4-6 Segmental vitiligo, on the other hand, represents localized vitiligo in a dermatomal
pattern (Figure 3, see page 342). This
type of vitiligo is more common in pediatric patients than in adults and is seen in
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3806Isenstein.indd 340
4% to 19% of children with vitiligo.2,4-6
Acrofacial vitiligo affects periorificial
areas and distal digits. It is less common still, seen in only 1% to 10% of patients.2,4,5 Universal vitiligo refers to the
complete depigmentation of the entire
skin and is very rare. Trichrome vitiligo
describes areas where different degrees
of depigmentation create a gradation of
skin color (Figure 4, see page 342).
In children, vitiligo most often presents
first on the head or neck.4,6,7 Other areas
of onset in descending order include the
trunk, lower extremities, and upper extremities.4,6,7 Often sites of trauma are favored
as demonstrated by frequent involvement
on the hands, elbows, and knees (Figure 1,
see page 339). Mucosal surfaces and hair
can also be affected.
The differential diagnosis of vitiligo in
children is limited (see Sidebar).3 Tinea
versicolor, a superficial yeast infection,
typically affects the chest and upper back
and has a fine scale that can be visualized with lateral pressure applied to the
hypopigmented area. Pityriasis alba, illdefined hypopigmented macules, is typically on the face and upper torso of children with atopic dermatitis. Vitiligo of
the genitals can be difficult to distinguish
from lichen sclerosus, an inflammatory skin condition that causes atrophy.
Postinflammatory hypopigmentation results from prior inflammation. These patients will have a history of rash or skin
condition localized to and preceding the
hypopigmented area. It is extremely rare
for vitiligo to present at birth, differentiating it from congenital lesions such as ne-
vus depigmentosus, nevus anemicus, ash
leaf macules of tuberous sclerosis, and
midline depigmentation of piebaldism.
EPIDEMIOLOGY
The mean age of onset of pediatric vitiligo is 4 to 8 years.2,4,5,7 Some data sets suggest females may be more commonly affected than males, but this difference may
reflect a reporting bias.4 Vitiligo affects all
races. However, it is more noticeable in
darker skinned individuals.
A family history of vitiligo is seen in
12% to 35% of pediatric patients with vitiligo,2,4,5,7 with an extended family history
of vitiligo being associated with earlier age
of onset.6 Affected children are more likely
to have a family member with a history of
premature graying of the hair, also known
as leukotrichia. Additionally, family members are more likely to have autoimmune
disorders such as thyroid disease, rheumatoid arthritis, inflammatory bowel disease,
alopecia areata, type 1 diabetes mellitus,
systemic lupus, multiple sclerosis, and pernicious anemia.2,4,6 Although vitiligo has
been associated with a family history of the
above autoimmune diseases, no specific autoimmune disorder appears to have a dominant relationship with pediatric vitiligo.
There has been much research exploring the association between vitiligo and
autoimmune diseases in those affected. In
children with vitiligo, concurrent cases of
alopecia areata, diabetes mellitus, thyroid
disease, Addison disease, and pemphigus
vulgaris have been reported.2 In adults,
there is an association between vitiligo
and autoimmune thyroiditis, also known
as Hashimoto’s thyroiditis.8 In children,
there may be an association between nonsegmental vitiligo and autoimmune thyroid
disease.5,9 Kakarou et al found that children
with vitiligo were 2.5 times as likely to develop Hashimoto’s thyroiditis compared
to healthy age- and sex-matched controls.5
Based on these findings, annual screening
for thyroid dysfunction and autoimmune
thyroiditis with a thyroid stimulating hormone, anti-thyroglobulin antibody, and
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TABLE 2.
Therapies for Vitiligo in Pediatric Patients
Therapy
Potent topical corticosteroids (clobetasol)
When and Where to Use
Risks
- < 20% BSA
- Atrophy, striae, telangiectases, hypertrichosis,
acne, HPA axis suppression
- Face, extremities, torso
- < 20% BSA
Calcineurin inhibitors (tacrolimus)
- Eyelids, face, intertriginous areas
Vitamin D derivatives (calciportriene)
- In combination with corticosteroids
- Burning sensation, malignancy, cost
- Segmental vitiligo of head and neck
Narrow-band UVB
Excimer laser
anti-thyroperoxidase antibody has been
suggested by some for all children with
vitiligo.5 However, other studies have failed
to establish an association between autoimmune thyroid disorders and pediatric
vitiligo and some pediatric dermatologists
screen for autoimmune thyroid disease in
asymptomatic patients only if the vitiligo is
extensive or there is a strong family history
of autoimmune disease.4,10
PATHOGENESIS
The pathogenesis of vitiligo is multifactorial. The aforementioned associations
of vitiligo with other autoimmune diseases
along with detection of antibodies and lymphocytes that recognize melanocyte antigens support an autoimmune etiology.3,11
Other theories include oxidative damage
to melanocytes or metabolic derangements
within melanocytes leading to apoptosis of
these pigment producing cells.12 The histopathology of vitiligo reveals a decreased
number or absence of melanocytes in affected skin compared to unaffected skin.
TREATMENT
Vitiligo is a visible disease that influences quality of life. Young adults with
a history of childhood vitiligo reported
teasing, being stared at, negative self-image, and feelings of shame.13 Those adults
with a history of childhood vitiligo and
the aforementioned negative experiences
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3806Isenstein.indd 341
- > 20% BSA
- Cases refractory to topical therapy
- Localized disease
are more likely to avoid participation in
sports, intimacy, and social activities, and
have more conflicts with their parents compared with adults with a history of childhood vitiligo who did not report negative
experiences.13 Adults with vitiligo reported
decreased body-image, self-esteem, and
quality of life as well.14 Psychological impact is greater in darker skinned people,
women, and when visible areas such as the
face and hands are involved.14 Screening
patients for psychological effects is recommended.3 We routinely ask our patients
and their families how the individual feels
about the skin condition and assess if other
children are teasing the child. Children
and families with psychological concerns
can be referred to a specialist for psychological evaluation and counseling. The National Vitiligo Foundation (www.nvfi.org)
provides information about local support
groups and other resources.
After discussion with the patient, no
treatment may be considered in patients
with fair skin. In these patients, the depigmented areas may not be noticeable and
therefore not impact the patient sufficiently
to warrant treatment. If repigmentation is
not pursued, it is still important to recommend regular sunscreen use as the depigmented areas sunburn easily.
For all patients with cosmetically deforming vitiligo, corrective camouflage
in the form of foundation and powder
- Irritation, cost
- Pruritus, dry skin, itching, time-intensive, cost
- Redness, blistering, cost
Figure 2. Vitiligo vulgaris. Well-demarcated depigmented patches on extensor lower legs.
should be offered to cover the depigmented areas. Advice on corrective camouflage can be found at the National
Vitiligo Foundation, Dermablend Website
(www.dermablend.com), and Cover Fx
Web site (www.coverfx.com). Patients
with vitiligo who were taught how to apply
corrective camoflauge reported substantial
improvement in their quality of life.15
Prior to initiating therapy for vitiligo,
it is important to discuss expectations.
Vitiligo is a chronic skin condition with
stable periods and intermittent flares.
Spontaneous repigmentation might oc-
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Drug Administration (FDA) approval
for the treatment of vitiligo. However,
all of the therapies have FDA approval
for at least one skin condition in adults
or adults and children.
Figure 3. Segmental vitiligo. Well-demarcated depigmented patch in a dermatomal distribution.
Figure 4. Trichrome vitiligo. Three shades of pigmentation in this early state of vitiligo (same patient as Figure 3 when she presented to our clinic).
cur in isolated areas.16 There is no evidence that treating vitiligo influences
its chronicity. Although a minority of
patients will have 100% repigmentation
with treatment, most will not. In most
studies, 75% repigmentation defines
successful treatment. Certain geographic regions including the head and neck
and hair bearing areas are more likely to
repigment than others such as the distal
extremities.17,18,22 Segmental vitiligo is
thought to be more difficult to treat compared to the other subtypes.
In patients who pursue treatment,
consider subtype of vitiligo, location
and extent of involvement when choosing therapy (see Table 2, page 340).
Other factors to consider include cost,
tolerability, and availability of treatment. No topical therapy has Food and
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3806Isenstein.indd 342
TOPICAL CORTICOSTEROIDS
Potent topical corticosteroids have
shown benefit in repigmenting vitiligo
in pediatric patients (see Figure 5, page
343). Lepe et al demonstrated 49.3%
mean repigmentation with the use of
clobetasol (Temovate) 0.05% ointment
twice daily for 2 months in a double
blind randomized trial.17 Similarly, in a
retrospective review of pediatric patients
with vitiligo, Cockayne et al reported
improvement or resolution of vitiligo
in children treated with topical steroids
over 2 months to 2 years.18 Repigmentation with topical corticosteroids tends to
be most successful on the face and in areas with greater density of hair follicles.
The main side effects of topical corticosteroids are atrophy and telangiectases, seen in 15% and 10% of the patients, respectively.17 Hypertrichosis and
acneiform eruptions are other known
cutaneous side effects of topical corticosteroids. Rarely, hypothalamic pituitary
adrenal axis suppression, Cushing’s
syndrome, and intracranial hypertension
have been reported in children receiving
topical corticosteroids.19-21
Potent topical corticosteroids should
be considered for treating vitiligo involving less than 20% body surface
area or when treatment is focused to
cosmetically sensitive areas.22 Regular
monitoring for evidence of atrophy, especially in thin skinned areas such as
the eyelids, face, and intertriginous areas is advised. Some recommend treatment with potent topical corticosteroids
for no more than 2 months.3 Others recommend alternating 6 to 8 week cycles
of class I corticosteroids followed by
class V corticosteroids.22 Clobetasol is
FDA approved for steroid responsive
dermatitis in adults but not in children.
TOPICAL CALCINEURIN INHIBITORS
Tacrolimus (Protopic) is an immunosuppressive that blocks the action of calcineurin leading to deceased transcription
of cytokines. Multiple case reports and
studies have demonstrated efficacy of tacrolimus in repigmenting vitiligo.17,23-25
Grimes et al reported a series of six patients, including three children, who repigmented with tacrolimus 0.03% and 0.1%
applied twice daily.23 In a randomized trial
comparing tacrolimus 0.1% ointment with
clobetasol 0.05% ointment, areas treated
with tacrolimus had a 41.3% mean repigmentation rate.17 Silverberg et al reported
a retrospective review of 57 children with
vitiligo treated with tacrolimus 0.03% and
0.1% ointment.24 Head and neck lesions
were more likely to repigment and repigmented to a greater extent compared to the
trunk or extremities. Additionally, 94% of
the cases of segmental vitiligo of the head
and neck repigmented to some degree with
tacrolimus application. Tacrolimus twice
daily dosing was more efficacious than
once daily dosing.
Side effects of tacrolimus include a
burning sensation with application, seen in
10% of the patients.17 No atrophy is appreciated. The long term effects of tacrolimus
are unknown. Chronic systemic immunosuppression is associated with increased
skin cancers and although this association
has not been demonstrated with topical tacrolimus, some suggest advising patients
being treated with topical tacrolimus to
practice sun protection.24 In 2006, topical
tacrolimus received a black box warning
for a potential cancer risk based on animal
studies and case reports.
Tacrolimus 0.1% ointment applied twice
daily should be considered in the treatment
of pediatric vitiligo involving less than 20%
body surface area and focused in cosmetically sensitive areas such as the face.3,26 In
particular, tacrolimus has a role in the treatment of vitiligo in atrophy sensitive areas
such as the eyelids and in segmental vitiligo of the head and neck. Tacrolimus 0.03%
ointment is FDA approved in children over
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the age of 2 with moderate to severe atopic
dermatitis. Tacrolimus 0.1% ointment is
FDA approved in adults with moderate to
severe atopic dermatitis.
TOPICAL VITAMIN D DERIVATIVES
Vitamin D derivatives such as calcipotriene (Dovonex) and calcipotriol have
been studied for the treatment of childhood vitiligo. Vitamin D derivatives have
immunomodulating characteristics and
may play a role in melanogenesis.27
Chiaverini et al reported 21 of 23
adult and pediatric patients with vitiligo
treated with calciportriol in a randomized study had no repigmentation after
3 to 6 months of therapy.28 Conversely,
Gargoom et al reported a prospective
open label study in which 10 of 18 children with vitiligo treated with calcipotriol twice daily had some degree of repigmentation.29 One patient complained of
irritation. Based on these reports along
with other studies in adults, the use of
vitamin D derivatives as monotherapy
for vitiligo is not recommended.3
Combination topical therapy of calcipotriene and corticosteroids for the
treatment of pediatric vitiligo may be
beneficial. Travis and Silverberg reported a series of 12 patients with pediatric
vitiligo treated with topical corticosteroids in the morning and calciportriene
in the evening.27 Eighty-three percent
of the patients repigmented. Eyelid and
facial skin repigmented best and no adverse events were reported. Calcipotriene is FDA approved for the treatment
of plaque psoriasis in adults.
PHOTOTHERAPY
Narrow-band UVB radiation has been
studied in children with vitiligo and has
a role in repigmentation, especially in
patients with greater 20% body surface
area affected and in vitiligo refractory
to topical treatments.3,30,31 Narrow-band
UVB radiation has a spectrum of 310315 nm with a maximum wavelength of
311 nm. Light therapy takes place two
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3806Isenstein.indd 343
Figure 5. Therapeutic response of segmental vitiligo to topical corticosteroids.
to three times a week at the doctor’s office in a phototherapy unit with multiple
light bulbs, similar in appearance to a
tanning bed in which the patient stands
upright. Eye protection is provided, unless eyelids are being treated, in which
case the patient keeps his eyes closed.
Each treatment lasts a few minutes. The
mechanism of action is thought to be
multifactorial with narrow-band UVB
halting further depigmentation and stimulating melanogenensis.
In an open trial, Njoo et al treated 51
children who had a mean affected body
surface area of 15% with narrow-band
UVB radiation twice weekly.30 Fiftythree percent had greater than 75% repigmentation. Lesions on the face and neck
responded best; lesions on the hands,
feet, fingers, and toes did not repigment
well. In addition to demonstrating repigmentation, the group measured improved
quality of life. Similarly, Brazzelli et al
reported an open uncontrolled trial of 10
children with vitiligo treated with narrow-band UVB radiation therapy twothree times per week.31 Five patients had
greater than 75% repigmentation.
Main side effects included itching,
dry skin and erythema. No phototoxic
or photoallergic reactions have been reported in children being treated with nar-
row-band UVB for vitiligo. There is no
early increased risk of developing skin
cancers in patients treated with narorowband UVB.32 However, long-term studies and studies in children are lacking.
Recently, the excimer laser has been
shown to be effective in repigmenting focal vitiligo. With a wavelength of 308 nm,
the excimer laser provides localized narrow-band UVB. In a retrospective review,
52% of 55 vitiligo lesions in 32 adult and
pediatric patients demonstrated greater
than 74% repigmentation with 8 to 30
laser treatments.33 As with narrow-band
UVB, lesions on the face responded best,
while lesions on the hands and feet were
least responsive. Darker skinned individuals repigmented more than their lighter
skinned counterparts. Initial studies of
combination therapy of topical corticosteroids with excimer and tacrolimus with
excimer appear superior to excimer laser
as monotherapy.34,35 Side effects of the excimer laser include redness and blistering.
No studies exploring skin cancer risk and
excimer laser have been published.
Topical psoralens with both natural
sunlight and UVA (topical PUVA), as well
as oral psoralens with UVA (oral PUVA)
have also been studied for the treatment
of vitiligo.36,37 Although effective, psoralens are phototoxic, and patients must
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be counseled to avoid exposure to sunlight
beyond the determined treatment time. Additionally, psoralens can cause nausea and
itching. In general, oral psoralens are not
recommended for children under 12 years
of age because of unknown long-term
effects. In a recent randomized, doubleblind clinical trial comparing narrow-band
UVB with oral PUVA, narrow-band UVB
repigmented a greater area, had better color match, and had fewer side effects. With
this study, narrow-band UVB supplanted
PUVA as the phototherapy treatment of
choice for vitiligo given its greater efficacy
and superior safety profile.
SURGICAL TREATMENT
Surgical treatment of vitiligo has not
been extensively studied in children and
adolescents. A case series of 10 adolescents
with 15 patches of vitiligo treated with suction blister epidermal grafts revealed that
86% of the lesions repigmented at least
75%.38 Adolescents had greater repigmentation compared to adults treated similarly.
Given the paucity of data on grafting in
children, surgical treatment is not a first
line therapy in pediatric patients.
CONCLUSION
Vitiligo is relatively easy to diagnose
but difficult to treat. Regular screening
of the psychosocial effects of vitiligo and
consideration of screening for autoimmune thyroid disease in children and adolescents with vitiligo is recommended. In
patients with less than 20% body surface
area involved, especially in cosmetically
sensitive areas, primary care providers
can initiate treatment with either potent
topical corticosteroids or tacrolimus. Primary care providers who are uncomfortable using these therapies should refer
their patients with vitiligo to a dermatologist. Additionally, patients who fail
to respond to topical therapy and those
with greater than 20% body surface area
involved should be referred to a dermatologist for evaluation and treatment with
combination therapy or phototherapy.
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