Clinical and epidemiological characteristics of childhood vitiligo a study of 701 patients from brazil

Report
Clinical and epidemiological characteristics of childhood
vitiligo: a study of 701 patients from Brazil
Clarissa Pereira dos Santos Martins, MD, MSc, Amanda Hertz, MD, MSc, Paulo Luzio, MD,
Patricia Paludo, MD and Luna Azulay-Abulafia, MD, PhD
Professor Rubem David Azulay Institute of
Dermatology, Vitiligo Clinic, Rio de Janeiro,
Brazil
Correspondence
Clarissa Pereira dos Santos Martins, MD,
MSc
Bar~
ao da Torre Street, number 445
apartment: 903 – Ipanema
Rio de Janeiro 22411-003
Brazil
E-mail: clapdsm@hotmail.com
Funding: None.
Conflict of interest: None.
doi: 10.1111/ijd.14645
Abstract
Background Vitiligo is an acquired pigmentary disorder that affects approximately 0.5–2%
of the world’s population, and 25% of cases begin before 10 years of age. Although
prevalent, there are few studies on the characterization of childhood vitiligo.
Objective To evaluate the clinical and epidemiological characteristics of childhood vitiligo.
Methods Transverse study conducted by reviewing data records of patients under the age
of 18 in which disease onset occurred before 13 years of age.
Results Predominance of females (62%). The most common subtype was generalized
vitiligo (53.8%). The average age of disease onset was 5.9 years. The most affected initial
site was head/neck (44.22%). The Koebner phenomenon was present in 38.2%, emotional
triggering factors in 67.0% of the patients, halo nevus in 17.4%, and associated
autoimmune disease in 6.5% of the patients. Family history of vitiligo was observed in
16.9% of the patients, and stability was reported by 20.1% of patients. The presence of
positive family history did not significantly influence the age of onset. We found a
significant difference between segmental vitiligo (SV) and nonsegmental vitiligo (NSV)
regarding the age of onset, Koebner phenomenon, hypothyroidism, anti-TPO antibodies,
family history of psoriasis, and halo nevus.
Conclusion Childhood vitiligo has its own characteristics. Vitiligo different subtypes have
distinct characteristics. Our study presents a great number of patients, helping to elucidate
the peculiarities of childhood vitiligo in the Brazilian population.
Introduction
Vitiligo is an acquired pigmentary disorder that results from a
progressive loss of functional melanocytes. The pathogenesis of
vitiligo is still unclear. It has been attributed to autoimmune-,
genetic-, and neuro-mediated aberrations. The prevalence of
vitiligo ranges from 0.06 to 2.28%, whereas in children/adoles-
cent populations it varies from 0.0 to 2.16% according to Kr€
uger
et al.1
In Brazil, Bechelli et al.2
reported a frequency of 0.04%
in schoolchildren. About half of affected patients have an onset
of disease before the age of 20 years.
The age limit used to define a case of childhood vitiligo varies
between studies from 12 to 16 years of age. Childhood vitiligo
differs from adult vitiligo in that it has a higher incidence in girls,
shows a higher incidence of segmental presentation, and has a
lower incidence of associated autoimmune and/or endocrine
diseases. Therefore, it has been considered a distinct subset of
vitiligo with a tremendous impact on the psychological develop-
ment of children.
Treatment options include topical (steroids, calcineurin inhibi-
tors, and vitamin D) or systemic medications (minipulse of oral
steroids and vitamins), phototherapy, corrective camouflage,
surgical grafting, or a combination of different treatment modali-
ties.3–5
In addition to providing a descriptive analysis of a large pedi-
atric vitiligo population, we compared clinical and laboratory
characteristics of segmental (SV) and nonsegmental vitiligo
(NSV).
Materials and methods
We performed a retrospective chart review of 701 patients. We
analyzed the clinical and laboratory data of patients with vitiligo
seen in the Vitiligo Clinic of Professor Rubem David Azulay
Institute of Dermatology (IDPRDA) in Rio de Janeiro, Brazil, a
tertiary referral center in which we provide treatment for cases
that were considered hard to manage and perform grafting
procedures depending on the clinical scenario. Patients under
the age of 18, in which disease onset occurred before 13 years
of age, were evaluated by our dermatologists between 2006
and 2014. Vitiligo was defined clinically, with the aid of Wood’s
lamp, as acquired depigmented lesions, after exclusion of other
ª 2019 The International Society of Dermatology International Journal of Dermatology 2019
1

differential diagnoses. For each patient, a standardized
evaluation, including a full clinical examination, was completed.
The Koebner phenomenon was considered if lesions were
present in areas of friction or if the parents reported their
occurrence at sites of previous trauma. Stability of vitiligo was
considered if the patient reported no new lesions and/or
enlargement of preexisting lesions in the period of 1 year.
Unilateral lesions that did not cross the midline and followed
Blaschko lines were classified as SV. Lesions in other
distributions were classified as NSV.
In order to classify patients with NSV, we used the revised
classification published in 2011 by the Vitiligo Global Issues
Consensus Conference (VGICC). Subjects were questioned
about the age at onset, site of onset, triggering factors,
presence of halo nevus, stability, Koebner phenomenon, and
personal and familial medical history of vitiligo, autoimmune
thyroid diseases, rheumatoid arthritis, type 1 diabetes mellitus,
psoriasis, pernicious anemia, collagenosis (rheumatoid arthritis
and systemic erythematous lupus), alopecia areata, and
premature hair graying (before the age of 30). Patients
underwent laboratory screening (serum thyroid-stimulating
hormone [TSH], serum T4 levels, antithyroglobulin and
antithyroperoxidase antibodies, antinuclear antibodies, and
antiparietal cell antibodies) at the time of inclusion in the study.
Laboratory tests were solicited to all; however, not all patients
went through laboratory testing, for personal reasons (i.e., fear
of needles, negligence of the parents, etc.), in spite of which,
data of all patients were computed and analyzed together as a
whole. The comparison of clinical and epidemiological
characteristics between NSV and SV was performed using the
v2
or Fisher’s exact test for categorical data and Student’s t test
for independent samples of numerical data. A P value of 0.05
was chosen to determine significance. Statistical analysis was
performed using software SAS, version 6.11 (SAS Institute,
Inc., Cary, North Carolina).
Results
Of the 701 children, 262 (37.4%) were boys and 439 (62%)
were girls, giving a male-to-female ratio of 1 : 1.67. The aver-
age age of onset was 5.9 years, and the average age of the
children studied was 11.9 years. In addition, eight children were
born with vitiligo (three with generalized vitiligo and five with
SV). The majority of our patients (51.1%) reported onset of viti-
ligo between 2 and 6 years of age (Table 1).
Of the 681 charts in which the clinical type of vitiligo was
available, 418 (61.4%) were classified as NSV, of which 366
(52.2%) cases were of generalized vitiligo. The second most
frequent subtype was SV (29.5%) followed by focal (5.7%),
acrofacial (4.6%), mucosal (2.3%), mixed (1.9%), and universal
vitiligo (1%). The most affected site of onset was the head/neck
segment (44.2%) (Table 2). Koebner’s phenomenon was
reported by 55.9% of patients with NSV; however, it was pre-
sent in only 10.6% and 6.4% of patients with segmental and
undetermined vitiligo, respectively (Table 3).
As to the precipitating factors, stress (such as school exami-
nations, too much homework, moving to another home,
divorced parents) was reported by 62.6% of patients with SV,
69.5% of patients with NSV, 62.8% of patients with undeter-
mined vitiligo, and by 67% of all patients.
Of the 701 patients inquired, 6.7% (n = 47) knowingly had an
autoimmune disease at the first visit. The inquiry of comorbidi-
ties and personal history of autoimmune disease in NSV
patients revealed that 29 (9.8%, n = 295) patients had
Table 1 Demographic characteristics of clinical types of vitiligo
Category
Total Segmental Nonsegmental Undetermined
n % n % n % n %
Sex
Masculine 262 37.4 88 42.5 146 35.4 15 26.8
Feminine 439 62.6 119 57.5 270 64.6 41 73.2
Age (years) 11.9 4.0 11.3 4.0 12.2 3.9 12.2 13.9
2–6 70 10.4 28 13.8 36 9.1 2 3.7
7–10 178 26.4 59 29.1 97 24.4 14 25.9
11–14 225 33.3 62 30..5 142 35.7 16 29.6
15–18 202 29.9 54 26.6 123 30.9 22 40.7
Age of onset (years) 5.9 3.3 5.4 3.5 6.1 3.1 6.1 3.1
up to 2 50 7.3 25 12.4 21 55 1 1.9
2–6 346 51.1 106 52.5 215 53.0 22 40.7
7–10 210 30.8 47 23.3 133 32.8 21 38.9
11–13 73 10.7 24 11.9 36 9.0 10 18.5
Years of disease 6.1 3.4 6.0 3.7 6.2 3.3 6.2 3.3
Numerical data were expressed by mean standard deviation.
International Journal of Dermatology 2019 ª 2019 The International Society of Dermatology
Report Childhood vitiligo: a study of 701 patients Martins et al.
2

hypothyroidism, two (0.8%, n = 263) had hyperthyroidism, one
(0.9%, n = 117) had pernicious anemia, seven (2.9%, n = 244)
had alopecia areata, and one (0.3%, n = 241) had diabetes
mellitus type 1. Within the SV group, three (2.9%, n = 104) had
hypothyroidism and three (3.4%, n = 89) had alopecia areata.
In the undetermined vitiligo group, one (2.8%, n = 36) had
hypothyroidism. No patient reported psoriasis, rheumatoid arthri-
tis, or systemic erythematous lupus.
Halo nevus was diagnosed in 53 patients, of which 45 had
NSV, four had SV, and two had undetermined vitiligo (two
patients were not classified into a clinical subtype of vitiligo).
Stability was reported by 19.4% of patients with SV, 20.6% of
patients with NSV, and 16.7% of patients with undetermined
vitiligo.
Family history was considered up to the second-degree rela-
tive. The frequencies of family history of vitiligo, autoimmune
thyroid diseases, alopecia areata, type 1 diabetes mellitus, col-
lagenosis (rheumatoid arthritis and systemic erythematous
lupus), psoriasis, and premature hair graying in each subtype of
vitiligo are presented in Table 4.
Part of the patients went through laboratory screening.
Table 5 discriminates the frequencies of antithyroid antibodies,
antinuclear antibodies, and antiparietal antibodies in each clini-
cal subtype of vitiligo. There was no significant difference in the
sex ratio between SV and NSV (P = 0.085, OR = 1.35). The
age of onset was earlier (P = 0.049) in SV (5.4 3.5) com-
pared to NSV (6.1 3.1).
The Koebner phenomenon was more frequently noted in
patients with NSV (P 0.0001; OR = 0.093) than in patients
with SV (Table 6).
We found a statistically significant difference (P 0.025)
when comparing the presence of hypothyroidism between SV
(2.9%) and NSV (9.8%) patients. There was no difference
between groups when we compared history of hyperthyroidism,
pernicious anemia, alopecia areata, psoriasis, diabetes mellitus
type 1, and collagenosis.
The presence of antithyroperoxidase antibodies was signifi-
cantly associated with NSV (P = 0.012); however, there was no
significant difference when comparing antithyroglobulin antibod-
ies, TRAb, antiparietal cell antibodies, and ANA (Antinuclear
antibody) between SV and NSV (Table 7).
The presence of halo nevus was strongly associated with
NSV (P = 0.0001). There was no significant difference found
between clinical types of vitiligo when we analyzed emotional
triggering factors and stability. When comparing SV with NSV,
we only found the family history of psoriasis to be statistically
significant between groups (VS: 16.2% vs. NSV: 4.8%;
P = 0.011) (Table 7). Family history of vitiligo did not influence
the age of onset (P = 0.15), as the mean age of onset was
6.4 3.4 years in patients with family history of vitiligo and
5.8 3.3 years in patients without it.
Discussion and Conclusion
Studies investigating childhood vitiligo are scarce in Brazilian
and world literatures, especially with large populations. This fact
is worrisome, considering that vitiligo usually begins in child-
hood or young adulthood, with approximately half of the patients
having onset prior to the age of 20 years.6
In our study, we found a large predominance of females
(62%), in accordance with previous studies.7,8,17,20
In a Chi-
nese9
and in a Korean10
study, however, boys and girls were
affected equally. It has been suggested that a higher preva-
lence in girls may be explained by the fact that parents worry
more and tend to seek treatment for cosmetically disfiguring,
depigmenting patches more frequently in girls. Therefore, the
discrepancy in the distribution of the disease between genders
described in some ambulatory studies may mean a selection
bias. Lin et al.9
argue that these differences in sex ratios may
be because of differences in ethnicity and locations.
In earlier published reports7,11
on childhood vitiligo, general-
ized vitiligo was the most frequent type reported. In our study
as well, it was the most common clinical type, seen in 366
patients (53.8%). The percentage of SV in children has been
reported to vary from 4.6 to 32.5%.12
As in Jaisankar et al.,11
SV was the second most frequent presentation, occurring in
30.4% of our patients, followed by focal vitiligo in 5.9%. We
found a much lower frequency of focal vitiligo than Handa
et al.8
(14.4%), Hu et al.12
(34.6%), Carvalho et al.14
(46.5%),
and Nunes et al.15
(18.8%).
Earlier onset vitiligo tends to be more focal in nature, and the
percentage of patients who initially present with focal vitiligo
may decrease with age,16
so our low frequency of focal vitiligo
may mean that patients took longer to be referred or to seek
our clinic, since we are a tertiary care center. Other Brazilian
studies reported focal vitiligo to be the most frequent type, fol-
lowed by generalized vitiligo.14,17
These differences between
populations could be theoretically because of genetic factors or
the use of different classification criteria.
Table 2 Sites of onset
Site of onset n %
Head and neck 310 44.2
Abdomen 35 5.0
Armpits 11 1.6
Thorax 12 1.7
Buttocks 9 1.2
Genitalia 41 5.8
Back 22 3.1
Hands 24 3.4
Upper limbsa
16 2.3
Feet 58 8.3
Lower limbsb
110 15.7
N/A 54 7.7
a
Except hands.
b
Except feet.
Martins et al. Childhood vitiligo: a study of 701 patients Report 3

Universal vitiligo was the least common type seen in our
study population. Unlike in our study, Halder et al.,7
Jaisankar
et al.,11
and Nunes et al.15
reported the acrofacial form to be
the least common. The mean age of onset in our study was
5.9 years. In another Brazilian study with 73 children, it was
5.7 years.17
The age of onset has not varied much among dif-
ferent studies. An American7
study reported mean age of onset
of 4.6 years, a Korean study10
reported 5.6 years, a study in
Kuwait18
reported 6.2 years, and Indian6,11
studies reported 6.9
and 6.4 years. The peak incidence occurred between 2 and
6 years (30.8%). Most of the studies show the age of onset of
vitiligo to be most common between the ages of 4 and 8 years,
as reported by Agarwal et al.6
and Hu et al.13
Nicolaidou
et al.19
reported it between 5 and 8 years. Other Brazilian stud-
ies reported peaks between 4 and 6 years and between 6 and
10 years.17,20
Children with SV (5.4 3.5 years) were affected earlier than
those with nonsegmental (6.1 3.1 years), which was
consistent with the findings of Hu et al.13
However, Mazereeuw
et al.12
did not find a statistically significant difference between
the ages of onset of segmental (7.43 1.54 years) and non-
segmental (8.55 0.77 years) cases. No previous Brazilian
study in children analyzed this parameter.
The most frequent site of disease presentation in our sample
was the head and neck segment (44.2%) in accordance with lit-
erature, in both SV and NSV.10,11,17,18
We believe this presen-
tation to be more frequent because it is more easily noticeable
than other sites. It was followed by lower limbs (8.3%), similar
to findings by Nicolaidou et al.19
In Brazil, Silva et al.17
reported
head followed by genitals, and Nunes et al.15
reported upper
limbs followed by head and neck segment. Emotional distress
plays an important role in vitiligo pathogenesis.21
In our study,
stress was reported as a triggering factor in 62.6% of SV
patients and 69.5% of NSV patients, with no statistically signifi-
cant difference found between the groups. Interestingly, Lin
et al.9
reported stress in a higher proportion of children with SV
Table 3 Frequencies of Koebner phenomenon, comorbidities, and stability for each vitiligo subtype
category
Segmental Acrofacial Generalized Mixed Universal Focal Mucosal
n % n % n % n % n % n % n %
Koebner
Present 17 10.6 8 29.6 180 57.9 5 45.4 5 100 2 5.9 1 7.7
Absent 144 89.4 19 70.4 131 42.1 6 54.6 0 0 32 94.1 12 92.3
Emotional stress
Present 112 62.6 18 60.0 251 71.9 6 50.0 1 16.7 24 64.9 8 57.1
Absent 67 37.4 12 40.0 98 28.1 6 50.0 5 83.3 13 35.1 6 42.9
Hypothyroidism
Present 3 2.9 0 0 24 9.3 1 11.1 4 66.7 1 4.0 0 0
Absent 101 97.1 21 100 235 90.7 8 88.9 2 33.3 24 96.0 11 100
Hyperthyroidism
Present 0 0 0 0 2 1 0 0 0 0 0 0 0 0
Absent 99 100 21 100 226 99 9 100 5 100 23 100 10 100
pernicious anemia
Present 0 0 0 0 1 1 0 0 0 0 0 0 0 0
Absent 55 100 8 100 104 99 4 100 0 0 11 100 4 100
Alopecia areata
Present 3 3.4 1 5.0 5 2.4 1 11.1 0 0 0 0 0 0
Absent 86 96.6 19 95.0 207 97.6 8 88.9 5 100 18 100 10 100
Halo nevus
Present 4 5.3 2 14.3 43 26.1 0 0 0 0 2 9.1 0 0
Absent 72 94.7 12 85.7 122 73.9 6 100 3 100 20 90.9 7 100
Psoriasis
Present 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Absent 54 100 8 100 95 100 5 100 0 0 12 100 5 100
Diabetes mellitus type 1
Present 0 0 0 0 0 0 0 0.0 0 0 0 0 0 0
Absent 89 100 19 100 210 100 6 100 5 100 18 100 10 100
Collagenosis
Present 0 0 0 0 0 0 0 0 0 0 0 0 0 0
Absent 89 100 19 100 210 100 8 100 5 100 19 100 10 100
Stable
Yes 33 19.4 4 17.4 63 21.1 2 18.2 0 0 5 15.6 3 18.8
No 137 80.6 19 82.6 235 78.9 9 81.8 3 100 27 84.4 13 81.2
4

(10 of 22 cases; 45.45%) compared with other vitiligo types.
The authors argued that this fact could imply that the pathogen-
esis of SV may be neuropsychologically related.
The Koebner phenomenon was reported by 38.2% of our
patients, similarly to the findings of another Brazilian study22
in
childhood vitiligo (23.4%) and other pediatric studies conducted
in India6
(24.3%) and in Kuwait18
(23.9%). However, other
authors reported much lower rates like Handa et al.8
(11.3%),
Nunes et al.15
(12.9%), and Lin et al.9
(5.1%). Handa et al. con-
sidered it surprising to find lower rates of Koebner, since chil-
dren are more likely to subject their skin to trauma while playing
and hence are more likely to develop koebnerization of the skin.
In our sample, 55% of NSV patients (57.9% of which had
generalized vitiligo) and 10.6% of SV patients reported the
Table 4 Frequencies of family history in each vitiligo subtype
Category
n % n % n % n % n % n % n %
FH of vitiligo
Yes 26 17.5 3 12.0 47 19.4 1 11.1 1 50.0 3 9.1 1 7.1
No 123 82.6 22 88.0 195 80.6 8 88.9 1 50.0 30 90.9 13 92.9
FH of thyroid disease
Yes 45 36.6 6 26.1 73 29.1 2 22.2 1 20.0 7 28.0 2 20.0
No 78 63.4 17 73.9 178 70.9 7 77.8 4 80.0 18 72.0 8 80.0
FH of alopecia areata
Yes 9 7.9 3 17.7 19 9.4 0 0 1 33.3 2 8.0 0 0
No 105 92.1 14 82.3 182 90.6 6 100 2 66.7 23 92.0 8 100
FH of Diabetes mellitus type 1
Yes 3 2.7 1 5.3 6 3.1 0 0 0 0 2 8.0 2 22.2
No 108 97.3 18 94.7 187 96.9 5 100 2 100 23 92.0 7 77.8
FH of collagenosis
Yes 4 3.5 1 6.3 12 6.0 1 14.3 0 0 1 4.0 0 0
No 112 96.5 I5 93.7 187 94.0 6 85.7 2 100 24 96.0 9 100
FH of psoriasis
Yes 11 16.2 1 11.1 4 4.3 0 0 0 0 1 7.7 1 10.0
No 57 83.8 8 88.9 88 95.7 3 100 1 100 12 92.3 9 90.0
FH of premature hair graying
Yes 31 22.1 6 33.3 50 22.8 2 25.0 2 50.0 6 25.0 5 41.7
No 109 77.9 12 66.7 169 77.2 6 75.0 2 50.0 18 75.0 7 58.3
FH, family history.
Table 5 Frequencies of autoantibodies in each vitiligo subtype
Category
n % n % n % n % n % n % n %
Anti-TPO
Altered 0 0 0 0 15 19 0 0 2 66.7 2 16.7 1 33
Normal 23 100 5 100 63 81 1 100 1 33.3 10 83.3 2 67
Anti-Tg
Altered 1 4.3 0 0 11 16.2 0 0 0 0 2 20.0 1 50.0
Normal 22 95.7 5 100 57 83.8 2 100 3 100 8 80.0 1 50.0
TRAb
Altered 1 9 0 0 0 0 0 0 0 0 0 0 0 0
Normal 10 91 4 100 I5 100 0 0 1 100 1 100 1 100
Antiparietal cell
Positive 1 17 0 0 0 0 0 0 0 0 0 0 0 0
Negative 5 83 4 100 21 100 1 100 3 100 3 100 2 100
ANA
Positive 3 30.0 1 20.0 15 37.5 0 0 1 50.0 3 50.0 1 33.3
Negative 7 70.0 4 80.0 25 62.5 3 100 1 50.0 3 50.0 2 66.7
Anti-TPO, Anti-thyroid peroxidase antibody; Anti-Tg, Antithyroglobulin antibody; ANA, Antinuclear antibody; TRAb, TSH receptor antibody.

Koebner phenomenon. We found statistically significant differ-
ence between the groups (P 0.0001; OR: 0.093). Convergent
results were obtained by Mazereeuw et al.,12
which reported
Koebner in 42.1% of patients and also found a higher frequency
in NSV (74.19% vs. 25%; P = 0.03).
Vitiligo has been associated with a number of endocrinopa-
thies and autoimmune disorders.6
Huggins et al.23
considered
children generally healthy nonetheless; the only autoimmune
disease commonly associated with pediatric NSV is autoim-
mune thyroiditis. The link between vitiligo and thyroid disease
Table 6 Comparison of frequencies of Koebner phenomenon, emotional stress, comorbidities, autoantibodies between
segmental and nonsegmental vitiligo
category
Segmental Nonsegmental
P value OR 95% CI
n % n %
Koebner
Present 17 10.6 198 55.9 0.0001 0.093 0.05–0.16
Absent 144 89.4 156 44.1
Emotional stress
Present 112 62.6 276 69.5 0.10 0.73 0.51–1.06
Absent 67 37.4 121 30.5
Hypothyroidism
Present 3 2.9 29 9.8 0.025 0.27 0.08–0.91
Absent 101 97.1 266 90.2
Hyperthyroidism
Present 0 0 2 0.8 0.53 n/a
Absent 99 100 261 99.2
Anti-TPO
Altered 0 0 17 19.5 0.012 n/a
Normal 23 100 70 80.5
Anti-Tg
Altered 1 4.4 11 14.1 0.18 0.28 0.03–2.27
Normal 22 95.7 67 85.9
TRAb
Altered 1 9.1 0 0 0.36 n/a
Normal 10 90.9 20 100
Pernicious anemia
Present 0 0 1 0.9 0.68 n/a
Absent 55 100 116 99.1
Antiparietal cell
Positive 1 16.7 0 0 0.17 n/a
Negative 5 83.3 29 100
Alopecia areata
Present 3 3.4 7 2.9 0.52 1.19 0.30–4.71
Absent 86 96.6 239 97.1
Halo nevus
Present 4 5.3 45 23.9 0.0001 0.18 0.06–0.51
Absent 72 94.7 143 76.1
Psoriasis
Present 0 0 0 0 n/a
Absent 54 100 108 100
DM 1
Present 0 0 1 0.4 0.73 n/a
Absent 89 100 240 99.6
Collagenosis
Present 0 0 0 0 n/a
Absent 89 100 242 100
ANA
Positive 3 30.0 17 34.0 0.56 0.83 0.19–3.63
Negative 7 70.0 33 66.0
OR, odds ratio; CI, Confidence interval (CI was 95%); n/a, not applicable; Anti-TPO, Anti-thyroid peroxidase antibody; Anti-Tg, Antithyroglobu-
lin antibody; ANA, Antinuclear antibody; TRAb, TSH receptor antibody; DM 1, Diabetes mellitus type 1.
Numerical data were expressed by mean standard deviation and compared by the Student’s t test for independent samples.
6

has been well established in adult patients; however, few and
controversial data have been reported about the association of
vitiligo and autoimmune thyroiditis in pediatric populations.6
In the present study, we found that 7.4% of patients (3 with
SV, 29 with NSV, and 1 with undetermined vitiligo; n = 33/448)
had hypothyroidism and 0.5% (two patients with NSV; n = 263)
had hyperthyroidism. We found a statistically significant differ-
ence (P = 0.025) when we compared the frequency of hypothy-
roidism between SV (2.9%) and NSV (9.8%). On the contrary,
Mazereeuw et al.12
described that history of autoimmune dis-
ease was found only in children with NSV with no significant dif-
ference between SV and NSV groups.
Previous studies in different countries reported higher fre-
quencies of thyroid diseases in children with vitiligo: Pagovich
et al.24
identified 25% of cases of active thyroid disease, Kak-
ourou et al.25
reported that 24.1% of children with vitiligo had
autoimmune thyroiditis, Nicolaidou et al.19
reported thyroid dis-
eases in 18% of patients, Agarwal et al.6
described thyroid dis-
orders in 9% of children, and Iacovelli et al.26
reported that
10.74% of children had thyroid dysfunction. Pediatric studies in
Brazil reported a very low frequency17
(2.3%) or no association
with thyroid disease. The differences in the rates reported may
be attributed to variations in the prevalence of thyroid disease
in different countries and within different regions of the same
country.
An increased incidence of autoantibodies without further evi-
dence of disease has been reported in children with vitiligo
compared with healthy children.12
The main antithyroid autoanti-
bodies detected in autoimmune diseases are TRAb, anti-Tg,
and anti-TPO, the most associated with clinical thyroid dysfunc-
tion.15
In Halder et al.7
and Schallreuter et al.,28
increased
serum thyroid autoantibodies positivity was found in 20% and
12% of patients, respectively.
We found antithyroid antibodies in a total of 36 patients, of
which 20 had anti-TPO (15.9%, n = 126), 15 had anti-Tg
(13.2%, n = 114), and one had TRAb (2.9%, n = 34). In our
research, only anti-TPO antibodies were strongly associated
with NSV (NSV = 19.5% vs. SV = 0%; P = 0.012). There was
no statistically significant difference between NSV and SV when
we compared the frequencies of antithyroglobulin antibodies,
TRAb, antiparietal cell antibodies, and antinuclear antibodies.
In contrast to our results, Mazzereeuw et al.12
detected
antithyroid (11.23%, n = 10/55) and antinuclear antibodies
(3.6%, n = 2/55) exclusively in NSV patients. Uncu et al. also
Table 7 Comparison of frequencies of family histories between segmental and nonsegmental vitiligo
Category
Segmental Nonsegmental
P valuea
OR 95% CI
n % n %
FH of vitiligo
Yes 26 17.4 52 18.7 0.75 0.92 0.55–1.54
No 123 82.6 226 81.3
FH of thyroid disease
Yes 45 36.6 82 28.5 0.10 1.45 0.93–2.27
No 78 63.4 206 71.5
FH of alopecia areata
Yes 9 7.9 23 10.1 0.50 0.76 0.34–1.70
No 105 92.1 204 89.9
FH of DM 1
Yes 3 2.7 7 3.2 0.55 0.84 0.21–3.32
No 108 97.3 212 96.8
FH of collagenosis
Yes 4 3.4 14 6.3 0.27 0.54 0.17–1.67
No 112 96.6 210 93.8
FH of psoriasis
Yes 11 16.2 5 4.8 0.011 3.86 1.28–11.7
No 57 83.8 100 95.2
FH of premature hair graying
Yes 31 22.1 60 24.1 0.66 0.90 0.55–1.47
No 109 77.9 189 75.9
Stable
Yes 33 19.4 69 20.6 0.75 0.93 0.58–1.48
No 137 80.6 266 79.4
OR, Odds ratio; CI, confidence interval (CI = 95%); FH, family history; Anti-TPO, Anti-thyroid peroxidase antibody; Anti-Tg, Antithyroglobulin
antibody; ANA, Antinuclear antibody; TRAb, TSH receptor antibody; DM 1, Diabetes mellitus type 1.
a
v2
test was used to compare categorial data.

found elevated thyroid antibodies solely in NSV patients, all of
which had elevated anti-TPO (8%, n = 4/50), whereas only one
also had elevated anti-TG (2%).
Silva et al.17
reported antithyroid antibodies in 3.4% (two of 59
patients) and antinuclear antibodies in 3.6% (two of 56 patients) of
the patients; however, the authors did not specify the types of anti-
bodies detected nor compared their frequencies between types of
vitiligo. Fernandes et al.26
did not detect anti-TPO, the only type of
antibody analyzed, in any of the sample patients (n = 50).
Antinuclear antibodies were detected in 24 patients (34.3%,
n = 70) and antiparietal cell antibodies in one patient (2.4%,
n = 41).
We observed an association between vitiligo and other
comorbidities such as pernicious anemia (0.5%; one case of
NSV), alopecia areata (2.7%; three cases of SV and seven
cases of NSV), and diabetes mellitus type 1 (0.3%, one case of
NSV). There were no cases of collagenosis or psoriasis. Few
data have been reported about associated comorbidities other
than thyroid disease in childhood vitiligo in world literature,
nonetheless, we found similar results to the available previous
studies. Halder et al.7
reported two cases (2.4%) of alopecia
areata in 82 children with vitiligo, Agarwal et al.6
reported alope-
cia areata (3.4%), psoriasis (1.5%), and diabetes mellitus
(3.3%). Nicolaidou et al.19
reported three cases (2.4%) of
rheumatoid arthritis and one case (0.8%) of alopecia areata.
Genetic factors are relevant in the pathogenesis of vitiligo.
Children with vitiligo have been reported to have a positive fam-
ily history of autoimmune/endocrine diseases more often, com-
pared with both children without vitiligo and adults with vitiligo.12
Family history of vitiligo in children with vitiligo wildly ranges
from 3.3 to 35% in various studies, which may be because of
the composition of the samples, sample sizes, and ethnic differ-
ences.6
In our data, there were 83 cases (16.9%) with a family
history of vitiligo (18.7% had NSV and 17.5% had SV) with no
significant difference between groups (P = 0.75).
The average age of onset (6.4 years) of children with a fam-
ily history of vitiligo was not earlier (P = 0.15) than of those
without a family history (5.8 years), in accordance with what Lin
et al.9
reported in a study with 620 children in China. However,
in the group described by Pajvani et al.,29
patients with vitiligo
and an extended family history of vitiligo were more likely to
have an earlier age of onset of disease than those with a nega-
tive family history (P = 0.024).
We also inquired patients about family history of thyroid dis-
ease, alopecia areata, diabetes mellitus, collagenosis, psoriasis,
and premature hair graying. When comparing SV with NSV, we
only found the history of psoriasis to be statistically significant
between groups (VS: 16.2% vs. NSV: 4.8%; P = 0.011). Interest-
ingly, in Greece, Nicolaiadou et al.19
also found that many of their
patients had a family history of psoriasis (16%; n = 20), although
the authors did not compare it’s frequencies in NSV and in SV.
Halo nevus was present in 53 (17.4%) of our patients and in
accordance with the findings of Lin et al.9
and Mazereeuw
et al.12
In our data, all types of vitiligo reported halo nevus,
including the segmental type (four cases). It was strongly asso-
ciated with NSV (NSV: 23.9% vs. SV: 5.3%; P = 0.0001). Maz-
ereeuw et al.,12
however, found no statistical significance
between the frequencies of halo nevus in NSV (20.22%) and
SV (12%) patients.
We found no significant difference when we compared the sta-
bility of the lesions between groups (NSV: 20.6% vs. SV: 19.4%;
P = 0.75). We argue that may be because parents seek medical
attention especially when lesions are increasing in number and/
or size, therefore the low percentage of stability may be because
of a selection bias. Mazereeuw et al.12
reported stability in
55.55% and 45.2% of patients with SV and NSV, respectively,
and found no statistically significant difference between groups.
In general, our results are partially in alignment with the world
literature. However, different populations have different particu-
larities because of distinct ethnicities and genetic backgrounds,
which justify the importance of regional studies.
The limitations of our study include those of any retrospective
study; noticeably, recall bias and nonrespondent bias. Incom-
plete charts and the fact that only part of our sample underwent
laboratory testing also may have limited our results. A selection
bias may also have influenced our results, since the study took
place in a tertiary referral center.
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