BASIC/CLINICAL SCIENCE

Effect of Age at Onset on Disease Characteristics in Vitiligo

Amrinder J. Kanwar, Rahul Mahajan, and Davindr Parsad
Background: Vitiligo is a multifactorial disease in which genetic, immunologie, and environrnental factors play an important part.
Late-onset vitiligo is a poorly defined entity.
Materials and Methods: Case records of patients who attended the pigmentary clinic at our institute from January 2001 to
December 2010 were reviewed. Patients with a diagnosis of vitiligo were analyzed with respect to their demographic characteristics
with special reference to their age at onset.
Results: Patients with disease onset after 30 years had a significantly higher association with precipitating factors such as
trauma, stress, and drugs in comparison with early-onset vitiligo (p < .004). However, the difference did not reach statistical
significance when these factors were analyzed individually. There was a significantly higher association with other nonautoimmune
diseases (p = .05), a higher incidence of positive family history (p < .0001), and a higher association with leukotrichia (p < .002) in
late-onset disease. Early-onset nonsegmental vitiligo was associated with a higher incidence of photosensitivity and pruritus
compared to early-onset segmental vitiligo.
Conclusion: Late-onset vitiligo has certain distinguishing features compared to early-onset vitiligo.
Contexte: Le vitiligo est une maladie plurifactorielle dans laquelle des facteurs gntiques, immunologiques, et
environnementaux jouent un rle important. Le vitiligo d'apparition tardive est une entit morbide mal dfinie.
Matriel et mthode: Ont t examins les dossiers de patients vus au service des troubles de la pigmentation, dans notre
tablissement, de janvier 2001 dcembre 2010. Les dossiers de ceux chez qui un diagnostic de vitiligo avait t pos ont fait l'objet
d'analyse pour ce qui est des caractristiques dmographiques, tout particulirement en ce qui concerne l'ge au moment de
l'apparition de la maladie.
Rsultats: II y avait dans le groupe de patients chez qui la maladie est apparue aprs la trentaine une association
significativement plus forte avec des facteurs dclenchants tels qu'un trauma, le stress, et les mdicaments que dans le groupe
de patients chez qui la maladie est apparue un ge prcoce (p < .004), mais la diffrence n'a pas atteint une signification statistique
dans l'analyse de ces facteurs pris individuellement. Toutefois, une association significativement plus forte avec d'autres affections
non auto-immunes (p = .05), une frquence plus leve d'antcdents familiaux positifs (p < .0001), et une association plus troite
avec la leucotrichie (p < .002) ont t notes dans les cas d'apparition tardive de la maladie. Le vitiligo non segmentaire d'apparition
prcoce tait associ une frquence accrue de photosensibilit et de prurit comparativement au vitiligo segmentaire d'apparition
prcoce.
Conclusion: Le vitiligo d'apparition tardive a certaines caractristiques qui le distinguent du vitiligo d'apparition prcoce:
y
lTILIGO is an acquired pigmentary disorder that is
associated with significant impairment in the quality
of life of those affected. The prevalence of vitiligo varies
From the Department of Dermatology, Venereology, and Leprology,
Postgraduate Institute of Medical Education and Research, Chandigarh,
India.
Address reprint requests to: Amrinder J. Kanwar, MD, FAMS, Department
of Dermatology, Venereology, and Leprology, Postgraduate Institute of
Medical Education and Research, Chandigarh 160012, India; e-mail:
ajkanwarl948@gmail.com.
DOI 10.2310/7750.2013.12075
2013 Canadian Dermatology Association
from 0.1 to 8% among different populations.' A great deal
of understanding regarding the pathogenesis has come
from the various epidemiologic studies and population
genetic linkage studies. Despite the plethora of knowledge
on vitiligo, evidence is still insufficient in certain areas,
such as late-onset vitiligo. Although the majority of
patients with vitiligo present in the second or third decade
of hfe, a significant number of cases manifest much later.
Currently, there is no consensus on the definition of early-
onset and late-onset vitiligo. In 2002, Burgos and
colleagues, based on the complex segregation analysis of
their patients, for the first time tried to define late-onset
vitiligo as disease starting after 30 years of age with a
DE C K E I^
C anadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 4 (July/August), 2013: pp 253-258
253
Kanwar et al
distinct human leukocyte antigen (HLA) haplotype
association.^ They attempted to explain the inheritance
pattern of vitiligo by classifying it into two groups: those in
whom the vitiligo inheritance followed a dominant pattern
of inheritance with incomplete penetrance, with an age at
onset of less than 30 years, and those in whom vitiligo
occurs after 30 years of age, which results from the mixed
effects of a recessive genotype and environmental events
that triggered the disease.
However, a decade after these observations were made,
there are few clinical data to support this hypothesis of two
distinct ages at onset in vitiligo. This research was
conducted to study the epidemiology of vitiligo in the
North Indian population over the past decade and to
further explore the above-mentioned but relatively less
studied phenomenon.
Materials and Methods
This was a retrospective study. Case records of patients
who had attended the pigmentary clinic at our institute
were screened for recruitment into the study during the
time period fi-om January 2001 to December 2010. All
patients with a clinical diagnosis of vitiligo of any subtype
were eligible for recruitment in the study. While making
the diagnosis of vitiligo and classifying it, the definitions
proposed by the Vitiligo European Task Force (VETF)
were taken into consideration.^ Segmental vitiligo of the
head and neck was further classified based on the
classification proposed by Gauthier and Taieb."*
A detailed history regarding the demographic char-
acteristics (age and sex), duration and evolution of the
disease, age and initial site of onset of disease, family
history, aggravating or initiating factors, associated
cutaneous or systemic illness, and the treatment given
was recorded. Clinical examination, including the extent of
body surface area involvement and the presence of
mucosal and hair involvement, was noted in all patients.
Statistical analysis was done using SPSS 17.0 (SPSS Inc,
Chicago, IL). The chi-square test was used to test the
homogeneity of the data with respect to age, gender, age at
onset, duration of illness, and body surface area involve-
ment and to determine any significant difference between
the demographic variables in various subgroups. A p value
< .05 was taken as significant.
Results
The case records of 1,416 patients were analyzed. Of these,
817 were males and 599 were females (M:F = 1.4:1). The
mean age of the study cohort was 23.78 14.98 years, the
mean age at onset was 14.7 14.19 years, and the mean
duration of illness was 8.54 9.93 years. The mean body
surface area involved was 7.21 11.09%. The most
common initial site of involvement was the face in 41.9%
of patients, of whom involvement of the eyelids was seen
in 12.9%. Nearly 13% patients attributed their disease
exacerbation to certain precipitating factors, of which
trauma was the most common in 6.6% of patients,
followed by stress such as pregnancy, surgery, or febrile
illness in 4.5% and drugs, including traditional medica-
tions, in another 1.9%. Apart from the cosmetic concern,
nearly 8.1% of patients experienced significant photo-
sensitivity and another 2.4% patients had associated
itching. A positive family history in a first- or second-
degree relative was elicited in 15.8% of patients.
Leukotrichia was observed in 21.6% of patients, and
mucosal involvement was seen in 20.6% of patients.
Nonsegmental vitiligo (NSV) was the most common
diagnosis in 78.1% of patients. Among these, generalized
vitiligo accounted for nearly 56.2% of all patients, and
acrofacial vitiligo was seen in 21.3%. Vitiligo universalis
was observed in a small minority of patients (0.5%).
Segmental vitiligo (SV) was seen in 7.2% patients, focal
vitiligo in another 9.4%, and mucosal vitiligo without
cutaneoiis involvement in 5.1% of patients.
In 116 (8.2%) patients, vitiligo was associated with
other cutaneous and systemic diseases. These were
classified as autoimmune diseases and nonautoimmune
diseases, and both of these groups were further subdivided
into systemic diseases and primary dermatologie diseases:
1. Autoimmune diseases. These were present in 45 (3.2%)
patients and included the following:
a. Primary dermatologie diseases (3; 0.2%). Alopecia
areata was present in 30.2% of patients.
b. Systemic diseases (42; 3%). Autoimmune diseases
such as hypothyroidism (14; 1%) and hyperthy-
roidism (4; 0.4%), diabetes mellitus (15; 1%),
allergic rhinitis (3; 0.2%), bronchial asthma (3;
0.2%), and idiopathic thrombocytopenic' purpura
(3; 0.2%) constituted the largest group associated
with vitiligo in 3% of patients.
2. Nonautoimmune diseases. These were present in 71
(5%) patients and included the following:
a. Primary dermatologie diseases (38; 2.6%). These
included dermatoses such as melasma (3; 0.2%),
acanthosis nigricans (2; 0.2%), cutaneous amy-
loidosis (3; 0.2%), lichen sclerosus et atrophicus
'254 Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 4 (July/August), 2013: pp 253-258
Early-Onset versus Late-Onset Vitiligo
(3; 0.2%), drug rash (3; 0.2%), pigmented pur-
puric dermatosis (3; 0.2%), idiopathie guttte
hypomelanosis (3; 0.2%), and palmoplantar hyper-
hidrosis (3; 0.2%). Leprosy was present in 3 (0.2%)
patients, and nevi such as halo nevi (6; 0.4%),
Becker nevus, nevus spilus, and port wine stain (3;
0.2% each) were present in 1% of patients,
b. Systemic diseases (33; 2.4%). Other nondermato-
logic systemic diseases that were associated
included hypertension (9; 0.6%), polycystic ovary
disease, osteoarthritis, and radiculopathy (present
in 3 [0.2%] patients each). Congenital diseases'
such as cryptorchidism and vaginal atresia were
present in 6 (0.4%) and 3 (0.2%) patients, and
infections such as tuberculosis were present in 3
(0.2%) patients.
However, the association of vitiligo with any of these
disorders was not statistically significant.
Early Onset yersus Late-Onset Vitiligo
We divided our cohort into two subgroups: early-onset
vitiligo < 30 years and late-onset vitiligo > 30 years. Of
1,416 patients, 1,211 (85.5%) had an early onset of'disease,
whereas 205 (14.5%) patients had late-onset vitiligo.
Table 1 shows the difterences in the demographic character-
istics of these two population subsets. It was observed that
patients with late-onset vitiligo had a significantly higher
association with precipitating factors in comparison with
early-oqset vitiligo (p = .004). Similarly, late-onset vitiligo
showed a significandy higher association with other diseases
(p < .0001), especially with other nonautoimmune diseases (p
= .04). A higher incidence of positive family history (p <
.0001) and a higher association with leukotrichia (p < .002)
were also observed in the late-onset group. The age at onset
also had a significant bearing on the initial site of onset, with
the face (30%) being the most common initial site in early-
onset disease compared to the hands (15%) in late-onset
disease. There were no difterences in the incidence of Koebner
phenomenon and mucosal involvement in the two subgroups.
Early- and Late-Onset NSV vs SV
Of 1,416 patients, 1,106 (78.1%) had NSV and 102 (7.2%)
had SV. The most common site of onset in both subgroups
was the face (26.6% in NSV and 30.4% in SV), followed by
the legs (17.9% in NSV and 17.6% in SV). Associated
diseases were seen in 8.1% in the NSV subgroup and 12%
in the SV subgroup (p = .05). A positive family history was
present in 15.4% of NSV patients and 12.4% of SV
Table 1. Age at Onset-Based Stratified Analysis of Demographic Characteristics of Study Population in Early-Onset and Late-Onset
Vitiligo
Demographic Characteristic
Age
TDI
M:F
Initial site of onset (%)
Precipitating factors (%)
Koebner phenomenon (%)
Stress (%)
Drugs (%)
Associated diseases (%)
Autoimmune diseases (%)
Systemic (%)
Primary dermatologie (%)
Nonautoimmune diseases (%)
Systemic (%)
Primary dermatologie (%)
Family history (%)
Leukotrichia (%)
Mucosa (%)
NSV VS SV (%)
NSV = nonsegmental vitiligo; SV =
*p < .05 = significant.
\
Early-Onset Vitiligo (n = 1,211)
19.87 11.58
9.18 10.31
1.32:1
Face 30.5; legs 19.9; trunk 10.2 Hands
14.4
6.3
6.7
1.4
7.3
3.2
2.9
0.3
4.1
1.7
2.4
14.4
20.7
19.4
81.1 VS 7.4
segmental vitiligo; TDI = total duration of illness.
Late-Onset Vitiligo (n = 205)
47.09 11.35
4.82 6.10
. 1.63:1
15; face 14.5; legs and lips 13.5 each
22.4
8.9
9.7
3.8
12.6
2.9
2.9
0.0
9.7
5.8
3.9
23.2
27.7
20.8
78.4 VS 4.5
P
.0001*
.0001*
.17
.0001*
.004*
.17
.6
.53
.0001*
.8
1.0
.9
.5
.09
.2
.0001*
.02*
.68
.31
! Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 4 (July/August), 2013: pp 253-258
255
Kanwar et al
patients. Symptoms such as pruritus and photosensitivity
were present in 10.6% of patients with early-onset NSV
compared to 6.7% in early-onset SV (p = .05).
Leukotrichia was present in 21.5% of NSV patients and
14.8% of SV patients. Mucosal involvement was seen in
23.7% of NSV patients and 19.9% of SV patients. Among
patients with SV, the lesions were localized to the head and
neck region in 35.9%, lower limbs in 26.2%, trunk in
18.7%, and upper limbs in 16.2%. Of these, 15.4% were in
the VI region of the head and neck, 6.7% in the V2 region,
3.1% in the V3 region, 6% in the V4 region, and 4.7% in
the V5 region. As stated above, we divided the cohort into
four subgroups based on the combination of diagnosis and
age at onset: early-onset NSV, late-onset NSV, early-onset
SV, and late-onset SV. Of 1,106 patients with NSV, 943
(85.2%) had early-onset NSV and 163 (14.8%) had late-
onset NSV. Of 102 patients with SV, 91 had early-onset SV
(89.2%) and 11 had late-onset SV (10.8%). Table 2
summarizes the observations seen in these subgroups.
Discussion
Vitiligo is a common depigmenting disorder that is
characterized clinically by circumscribed hypomelanosis of
the skin and hair and histopathologically by complete
absence of melanocytes. The disease can occur at any age
starting from infancy, but nearly 50% of patients have their
disease onset before the age of 20 years and 70 to 80% before
the age of 30 years. The mean age at onset is earlier in those
with a positive family history.^ The two most well-recognized
morphologic patterns of the disease are NSV and SV; others
are focal vitiligo, mucosal vitiligo, and universal vitiligo. The
most common sites involved are the fingers, hands, face, and
other trauma-prone areas of the body. The demographic
profile of patients in our study did not differ much from
other studies mentioned in the literature. The mean age at
onset was in the second decade of life ( 14.7 years), with nearly
85% of patients presenting before 30 years of age. A slight
male preponderance was observed, as seen in another study
from our center.^ In one of the largest epidemiologic studies
from Ghina involving 4,118 outpatients with vitiligo, the
mean age at vitiligo onset was 18.88 years, wdth more than
60% of patients being affected before 2 years of age.^
Patients wdth SV were affected earlier than those vnth other
types of vitiligo (15.55 years; p < .001). The percentage of
patients with a positive family history of vitiligo was 15.8% in
our study, which is consistent with other Indian studies.*'^''
However a lower prevalence of other associated cutaneous
and noncutaneous diseases (8.2%) was noted in our patient
population compared with previous studies.^
Table 2. Age at Onset-Based Stratified Analysis of Demographic Characteristics of Study Population in Early-Onset and Late-Onset
Nonsegmental and Segmental Vitiligo
Demographic Characteristic
M:F
Initial site of onset (%)
Precipitating factors (%)
Koebner phenomenon (%)
Stress (%)
Drugs (%)
Associated diseases (%)
Autoimmune diseases (%)
Systemic (%)
Primary dermatologie (%)
Nonautoimmune diseases (%)
Systemic (%)
Primary dermatologie (%)
Family history (%)
Leukotrichia (%)
Mucosa (%)
Early-Onset
NSV (n = 943)
1.32:1
Face 31.2; legs 20;
trunk 11.5
14.7
6.6
6.5
1.6
8.1
3.8
3.5
0.3
4.4
1.9
2.5
15.4
21.5
23.7
Early-Onset
SV (n = 91)
1.17:1
Face 34.1; legs 18.2;
lips and nape of neck
9.1 each
20.2
9
10.1
1.1
12
3.3
3.3
0
8.8
3.8
5
12.4
14.8
19.9
P
.817
.003*
.09*
.7
.21
.92
.05*
.81
.9
.9
.03*
.07
.02*
.39
.31
.13
Late-Onset
NSV (n = 163)
1.91:1
Hands 16.2; legs
14.9; face 13
24'
10.4
10.5
3.1
14.1
3.6
3.6
0
10.4
7.3
2.9
25.8
29.6
17.7
Late-Onset
SV (n = 11)
1:8
Hands 22.2; face.
arms, forearm.
trunk 11.1 each
0
0
0
0
27.2
0
0
0
27.2
0
27.2
22.2
22.2
18.6
P
.03*
.72
.0003*
.02*
.002*
.1
.9
.2
.2
.0
.02*
.2
.01
.66
.67
.34
NSV = nonsegmental vitiligo; SV = segmental vitiligo.
*p < .05 = significant.
Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 4 (July/August), 2013: pp 253-258
Early-Onset versus Late-Onset Vitiligo
Vitiligo has a strong genetic component; this was well
elucidated in a study by Alkhateeb and colleagues, who
found the frequency of vitiligo in the siblings to be about 18
times that in the population.'" However, in the same study,
the concordance of vitiligo in monozygotic twins was only
23%, indicating a significant nongenetic component.
Further case-control studies have reported a link between
NSV and genes (such as CTLA4, PTPN22, MBL2, ILIO, and
NALPl) already associated with autoimmune diseases."''^
Burgos and colleagues showed that HLA-DR4 is increased in
younger patients,^ whereas Orecchia and coUeagues observed
that HLA-DRw6 is more frequently found in patients with
an older age at onset.'^ The pdiatrie form of the disease is
strongly associated with HLA.B, C4A3, C4B1, DR5 (Wl 1),
and DQW3, whereas HLA-BfS, C4A3, C4B1, DR7, and
DQW2 are the markers of the adtilt form of the disease."*
In the present study, we classified our patients on the
basis of age at onset as vitiligo occurring before and after
30 years, although in an earlier study from our center, late-
onset disease was defined as disease occurring after 50
years.'^ We observed that patients presenting with late-
onset vitiligo had a significantly higher prevalence of
associated diseases, especially nonautoimmune diseases;
precipitating factors such as trauma, stress, and traditional
herbal medications; and a family history compared to
those with early-onset disease. These could be explained to
a certain extent by the part being played by environmental
factors such as medical illness, surgical trauma or stress,
pregnancy, and drugs, which may trigger the disease in
genetically predisposed individuals. Moreover, certain
diseases, such as hypertension and diabetes, are more
likely to occur after the third decade of life, which may be
the confounding factor in patients with late-onset vitiligo
having a higher prevalence of associated diseases.
There are limited data to which we can compare our
results as no consistent definition of early- and late-onset
vitihgo has been followed. Mazereeuw-Hautier and collea-
gues, while comparing the clinical features of NSV and SV in
114 children, found NSV to be associated with a higher
number of lesions, a larger body surface area of involve-
ment, a higher incidence of the Koebner phenomenon, and
the presence of thyroid abnormalities.'* In our study, we
found pruritus and photosensitivity to be present in 10.6%
of patients with early-onset NSV compared to 6.7% in early-
onset SV (p = .05). These findings are consistent with
observations made by Ezzedine and colleagues, who
compared the factors associated with early-onset SV and
NSV (defined as onset at less than 17 years).''' Of 213
children, patients with NSV showed a significantly higher
prevalence of halo nevi, a positive family history of vitiligo
and autoimmunity, and a higher prevalence of pruritus. In
our cohort, this difference was even more marked in late-
onset vitihgo (ie, 18.1% vs 11.1%), thus reinforcing the
belief that late-onset vitihgo has a strong environmental
component in its pathogenesis apart from the genetic
makeup. Another interesting observation was the signifi-
cantly higher prevalence of associated diseases in early-onset
SV compared to NSV. However, SV patients had a much
higher incidence of nonautoimmune diseases (p = .05),
which included both systemic diseases such as cryptorchid-
ism and vaginal atresia and primary dermatologie diseases
such as Becker nevus, compared to autoimmune diseases,
which were almost exclusively seen in NSV (p = .9). Park
and colleagues and Hann and Lee reported that nearly 9.5%
and 6.7% of SV cases, respectively, were associated with
other diseases.'^'" There were no significant differences in
the percentage of patients' showing leukotrichia between the
two subgroups, although it was lower than seen in other
studies.^" Dogra and colleagues defined late-onset vitiligo as
the disease occurring after 50 years of age.'^ In their study, a
slight female predilection was seen (87 males vs 95 females).
Associated autoimmune/endocrine diseases were seen in
21.4% of patients, which is comparable to 16.1% seen in the
present study. Finally, based on our observations, we
support the hypothesis that late-onset vitiligo should be
defined as disease occurring after 30 years of age.
There are few limitations to our study. Due to its
retrospective design, we had to rely on the accuracy of
record keeping for data collection. Civen that patients self-
reported their symptoms, recall bias (eg, in recollecting the
exact age at onset) might have a bearing oil the final
analysis. However, a uniform proforma was used to collect
data from all patients to ensure the homogeneity of the
data. Moreover, aU records were updated regularly and
safely stored. Another important flaw was the issue of
confounding in determining whether the association
between late-onset vitiligo and nonautoimmune diseases
was a true association or by chance. Due to the lack of age-
and sex-matched control population, we could not
establish a true association. Hence a prospective, con-
trolled study is needed to confirm the results of our study.
Conclusions
Late-onset vitiligo can be defined as vitiligo occurring after
the age of 30 years. It is a separate subset that manifests in
patients with a strong genetic background and the
presence of precipitating environmental factors. Hands
are the most common initial site to be involved, and the
disease onset may be preceded by a precipitating factor in a
' Canadian Dermatology Association I journal of Cutaneous Medicine and Surgery, Vol 17, No 4 (July/August), 2013: pp 253-258
257
Kanwar et at
significant proportion of patients. Late-onset disease is also
associated with a higher incidence of nonautoimmune
diseases.
Acknowledgment
Financial disclosure of authors and reviewers: None
reported.
References
1. Alikhan A, Feisten LM, Daly M, Petronic-Rosic V. Vitiligo: a
comprehensive overvievv' - part 1. Introduction, epidemiology,
quality of life, diagnosis, differential diagnosis, associations,
histopathology, etiology, and work-up. J Am Acad Dermatol
2011;65:473-91, doi:10.1016/).iaad.2010.11.061.
2. Burgos MA, Parodi E, Salgar M, et al. Vitiligo: complex segregation
and linkage disequilibrium analyses v^iith respect to microsatellite
loci spanning the HLA. Hum Genet 2002;l 10:334-^2, doi:10.1007/
S00439-002-0687-5.
3. Taieb A, Picardo M; VETF Members. The definition and assessment
of vitiligo: a consensus report of the Vitiligo European Task Force.
Pigment CeU Res 2007;20:27-35, doi:lp.Illl/j.l600-0749.2006.
00355.x. " "
4. Gauthier Y, Taieb A. Proposal for a new classification of segmental
vitiligo of the face [abstract]. Pigment Gell Res 2006;19:515.
5. Zhang Z, Xu SX, Zhang EY, et al. The analysis of genetics and
associated autoimmune diseases in Ghinese vitiligo patients. Arch
Dermatol Res 2009;301:167-73, doi: 10.1007/s00403-008-0900-z.
6. Handa S, Kaur 1. Vitiligo: clinical findings in 1436 patients.
J Dermatol 1999;26:653-7.
7. Liu JB, Li M, Yang S, et al. Glinical profiles of vitiligo in Ghina: an
analysis of 3742 patients. Clin Exp Dermatol 2005;30:327-31,
doi:10.1111/.1365-2230.2005.01813.x.
8. Halder RM. Ghildhood vitUigo. Glin Dermatol 1997; 15:899-906,
dpi:10.1016/S0738-081X(97)00131-4.
9. Haider RM, Grimes PE, Gowan GA, et al. Ghildhood vitiligo.
J Am Acad Dermatol 1987;16:948-54, doi: 10.1016/SOl90-9622(87)
70119-4.
10. Alkhateeb A, Fain PR, Thody A, et al. Epidemiology of vitiligo and
associated autoimmune diseases in Gaucasian probands and their
famUies. Pigment Gell Res 2003;16:208-14, doi:10.1034/j.l600-
0749.2003.00032.x.
11. Spritz RA. The genetics of generalized vitiligo and associated
autoimmune diseases. J Dermatol Sei 2006;41:3-10, doi: 10.1016/
.idermsci.2005.10.00i.
12. Picardo M, Taieb A. Pathophysiology overview. In: Picardo M,
Taieb A, editors. Vitiligo. 1st ed. New York: Springer; 2010. p. 149-52.
13. Orecchia G, Perfetti L, Malagoli P, et al. Vitiligo is associated with a
significant increase in HLA-A30, Gw6 and DQw3 and a decrease in
G4AQ0 in northern Italian patients. Dermatology 1992;185:123-7,
doi:10.1159/000247426.
14. Finco OM, Cuccia M, Martinetti G, et al. Age of onset in vitiligo:
relationship with HLA supratypes. Glin Genet 1991;39:48-54,
doi:10.1111/i.l399-0004.1991.tb02984.x.
15. Dogra S, Parsad D, Handa S, Kanwar AJ. Late onset vitiligo: a
study of 182 patients. Int J Dermatol 2005;44:193-6, doi:10.1111/
.1365-4632.2004.01948.X.
16. Mazereeuw-Hautier J, Bezio S, Mahe E, et al. Groupe de Recherche
Glinique en Dermatologie Pdiatrique (GRGDP). J Am Acad
Dermatol 2010;62:945-9, doi:10.1016/j.)aad.2009.06.081.
17. Ezzedine K, Diallo A, Leaute-Labrze G, et al. Multivariate analysis
of factors associated with early-onset segmental and nonsegmental
yitiligp: a prospective observational study of 213 patients. Br J
D,erniatol 2011;165:44-9, doi:10.1111/i.l365-2133.2011.10311.x.
18. Park K, Youn JL, Lee YS. A clinical study, of 326 cases of vitiligo.
Korean J Dermatol 1988;26:200-5.
19. Hann SK, Lee HJ. Segmental vitiligo: clinical findings in 208
patients. J Am Acad Dermatol 1996;35:671^, doi:10.1016/S0190-
9622(96)90718-5.
20. Song MS, Hann SK, Ahn PS, et al. Glinical study of vitiligo:
comparative study of type A and B vitiligo. Ann Dermatol 1994;6:
22-30.
Canadian Dermatology Association I Journal of Cutaneous Medicine and Surgery, Vol 17, No 4 (July/August), 2013: pp 253-258