Vitiligo in North-Eastern China: An association between mucosal and acrofacial lesions.

Abstract

Vitiligo is a mucocutaneous pigmentary disorder with worldwide distribution. Little is known about the clinical profile of vitiligo in North-eastern China. Accordingly, we reviewed 692 vitiligo out-patients from seven government hospitals in North-eastern China via a questionnaire in a multi-centre study conducted between June 2007 and June 2008, and hence characterized the epidemiology of vitiligo in North-eastern China. The mean +/- standard deviation age of onset was 23.69 +/- 13.83 years (range < 1-77 years). No gender preponderance was seen. The back was the most common site of involvement (39.6%). Vitiligo vulgaris was the predominant form (53.5%). Mucosal lesions were associated with lesions on the feet (odds ratio (OR) = 3.177, p < 0.001), hands (OR = 2.228, p < 0.01), face (OR = 2.028, p < 0.05) and neck (OR = 0.454, p < 0.05); but were not associated with chest, abdomen, waist, arms, legs or scalp lesions. Mucosal vitiligo is probably a special form of acrofacial vitiligo.

Full text

Page 1

Acta Derm Venereol 90
INVESTIGATIVE REPORT
Acta Derm Venereol 2010; 90: 136–140
© 2010 The Authors. doi: 10.2340/00015555-0799
Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555
Vitiligo is a mucocutaneous pigmentary disorder with
worldwide distribution. Little is known about the clinical
profile of vitiligo in North-eastern China. Accordingly, we
reviewed 692 vitiligo out-patients from seven government
hospitals in North-eastern China via a questionnaire in
a multi-centre study conducted between June 2007 and
June 2008, and hence characterized the epidemiology of
vitiligo in North-eastern China. The mean ± standard de-
viation age of onset was 23.69 ± 13.83 years (range < 1–77
years). No gender preponderance was seen. The back was
the most common site of involvement (39.6%). Vitiligo
vulgaris was the predominant form (53.5%). Mucosal le-
sions were associated with lesions on the feet (odds ratio
(OR) = 3.177, p < 0.001), hands (OR = 2.228, p < 0.01), face
(OR = 2.028, p < 0.05) and neck (OR = 0.454, p < 0.05); but
were not associated with chest, abdomen, waist, arms, legs
or scalp lesions. Mucosal vitiligo is probably a special form
of acrofacial vitiligo. Key words: vitiligo; epidemiology;
Chinese.
(Accepted October 14, 2009.)
Acta Derm Venereol 2010; 90: 136–140.
Xing-Hua Gao, Department of Dermatology, No. 1 Hos-
pital of China Medical University, 155 North Nanjing
Street, Heping District, Shenyang 110001, China. E-mail:
gaobarry@hotmail.com
Vitiligo involves a progressive loss of melanocytes from
the epidermis and hair follicles, making the integument
and sometimes hairs milky-white in appearance (1, 2).
There has been considerable controversy regarding the
aetiology and pathogenesis of vitiligo (3–5), though most
investigators now consider generalized vitiligo to be an
autoimmune disease. Owing to close resemblance in
histopathological characteristics, vitiligo has been likened
to hair greying, in which pigment loss in hair follicles
results from marked reduction in melanogenically-active
melanocytes in the hair bulb of grey anagen hair follicles
(6). Premature hair greying may be associated, among
other diseases, with vitiligo (7), although the relation-
ship between premature hair greying and vitiliginous
leukotrichia has not been studied. The relationship
between premature hair greying and a family history of
premature hair greying in vitiligo patients has also not
been well studied.
China has a population so diverse that the clinical and
epidemiological data obtained from one region of the
country may not accurately represent another region. The
Han ethnic group, which comprises more than 90% of
the Chinese population, has been the focus of many epi-
demiological studies conducted in China, whereas little
attention has been paid to regional variations in the clini-
cal profile of vitiligo elsewhere in China. North-eastern
China, for example, has a population of approximately
90 million people, but to the best of our knowledge, no
clinico-epidemiological data on vitiligo in this region are
available. Accordingly, in the present study, we obtained
clinico-epidemiological data on this disease in North-
eastern China, compared it with those obtained in other
parts of the world, and thus established a reference base
for this important region of the world.
PATIENTS AND METHODS
A total of 692 vitiligo out-patients from seven government hos-
pitals in North-eastern China were reviewed via a questionnaire
in a multi-centre study conducted between June 2007 and June
2008. A confirmed clinical diagnosis of vitiligo was required
for a patient to be included in this study. Patients with other
forms of leukoderma were excluded. The same general ques-
tionnaire form was used for all patients in all the centres, and
training was provided to all the assessors prior to the study. The
questionnaire itself queried information that included patient’s
name, age, sex, address, telephone number, marital status, self-
described ethnic group, age of disease onset, family history of
vitiligo and family or personal history of thyroid disease and
other autoimmune diseases, such as alopecia areata, rheumatoid
arthritis, diabetes, and pernicious anaemia. Distribution of the
patient’s lesions and extent of disease, disease stage and dura-
tion, level of activity, and previous episodes of repigmentation
were also recorded. Follow-up telephone interviews were used
to complete missing or inconsistent items. Questionnaires with
missing or inconsistent items that could not be corrected by
telephone interviews were excluded.
We grouped the patients into six vitiligo types: vulgaris, acro-
facial, focal, segmental, universal, and mixed: in accordance with
the standard working classification of clinical types of vitiligo.
Onset age was defined as the age at which the first white spot
was observed by the patient and confirmed by a dermatologist
as vitiligo.
To improve reliability and data accuracy, 249 patients seen in
one of the centres (No. 1 Hospital of China Medical University)
were further analysed for premature hair greying, vitiliginous
leukotrichia, Koebner’s phenomenon, halo phenomenon, and
other risk factors during the same study period. These pa-
tients were interviewed by the same assessor using a longer
version of the questionnaire, which included the items in the
Vitiligo in North-eastern China: An Association between Mucosal
and Acrofacial Lesions
Uwesu Omari MCHEPANGE1, Xing-Hua GAO1, Yue-Yang LIU2, Yu-Bo LIU1, Lei MA1, Li ZHANG1 and Hong-Duo CHEN1
Department of Dermatology, 1No. 1 Hospital of China Medical University and 2Shenyang No. 7 People’s Hospital, Shenyang, China

Page 2

137
Vitiligo in North-eastern China
general questionnaire mentioned above and, additionally spe-
cial questions concerning premature hair greying, vitiliginous
leukotrichia, etc.
Premature hair greying was defined as hair greying before age
25 years or, alternatively, a self-report that the subject’s hair had
turned more than 50% grey before age 40 years (6–8). We care-
fully examined our patients to exclude those with hair greying on
lesional skin, especially for vitiligo involving scalp skin, which we
regarded strictly as vitiliginous leukotrichia. We also excluded the
occasional few grey hairs that may develop in children.
Statistical analysis of the results was carried out using the
Statistics Package for Social Sciences (SPSS, version 13.0) for
Windows. Statistical analyses, such as frequencies, cross tabs
and non-parametric tests, were performed, and a level of p < 0.05
(two-tailed) was considered statistically significant.
RESULTS
General information
The mean ± SD age of the patients at the time of study
was 26.90 ± 14.80 years and the age range 3–77 years.
Overall, 93.8% (n = 649) of study cases were of the Han
ethnic group, while non-Han Chinese comprised 6.2%
(n = 43) of cases. A total of 268 (38.7%) of visits were
new cases (first diagnosis) and 424 were old cases, of
which 315 (45.5%) presented due to a persistent di-
sease and 109 (15.8%) due to relapse after a previous
disease-free period.
In 50.6% (n = 350) of cases lesions were still expan-
ding or spreading at the time of the visit (progressive
course), 44.8% (n = 310) of cases had stable lesions,
and 4.6% (n = 32) of cases reported lesions that were
decreasing in number or size (regressive course). The
mean disease duration was 30.58 ± 55.38 months for
those in progressive stage, 42.52 ± 95.03 months for
those in stable stage and 28.91 ± 44.78 months for those
in regressive stage. The overall mean disease duration
was 35.85 ± 75.58 months (range 1 month–50 years).
Onset age, site and vitiligo types
The earliest age of disease onset was before the
patient’s first birthday, and the latest was at age 77
years mean 23.69 ± 13.83 years and median 21 years.
The mean onset age was 22.82 ± 13.08 years (median
20, range < 1–76) for male patients and 24.68± 14.61
years (median 22, range 2–77) for female patients.
Male patients (n = 369; 53.3%) slightly outnumbered
female patients (n = 323; 46.7%); this difference was
not statistically significant. Overall, vitiligo vulgaris
was the predominant type (53.5%), followed by focal
(32.5%), acrofacial (6.8%), mixed (6.0%), universal
(2.7%), and segmental (0.7%) types. Both sexes had
equal chances of acquiring any of the types mentioned
above (p = 0.227, Fig. 1).
The most common site of disease involvement was
the back (39.6%). Other commonly involved sites were
the face (35.3%), chest (32.8%), legs (32.2%), abdomen
(31.9%), neck (31.4%), hands (29.2), arms (27.5%),
waist (22.0%), feet (15.0%), scalp (11.3%) and oral,
nasal and genital mucosae (8.8%).
We found that mucosal involvement was associated
with involvement of the feet (OR = 3.177, χ2 = 16.519,
p < 0.001), hands (OR = 2.228, χ2 = 9.038, p < 0.01), face
(OR = 2.028, χ2 = 7.095, p < 0.01), and neck (OR = 0.454,
χ2 = 5.519, p < 0.05). Mucosal involvement was not as-
sociated with involvement of the chest, abdomen, back,
waist, arms, legs or scalp (Table I). As for the neck,
which is not part of acrofacial vitiligo, the OR value of
0.454 shows that lesions on the neck were protective
for mucosal vitiligo. Considered together, these results
suggest that “mucosal vitiligo”, as proposed by some
authors, may be a special form of acrofacial vitiligo.
Fig. 1. Distribution of vitiligo types by gender in North-eastern China.
Table I. Association of mucosal vitiligo with vitiligo involving other
sites, in North-eastern China
Sites involved
(cross-tabulated)
Mucosa * Scalp
Mucosa * Face
Mucosa * Neck
Mucosa * Chest
Mucosa * Back
Mucosa * Abdomen
Mucosa * Waist
Mucosa * Arm
Mucosa * Leg
Mucosa * Hand
Mucosa * Foot
OR value
1.821
2.028
0.454
0.644
0.613
0.961
0.675
1.207
1.304
2.228
3.177
Pearson χ2
2.896
7.095
5.519
2.047
2.846
0.019
1.212
0.421
0.920
9.038
16.519
Significance
(2-tailed)
0.089
0.008
0.019
0.153
0.092
0.890
0.272
0.517
0.338
0.003
0.000
OR: odds ratio
Acta Derm Venereol 90

Page 3

138
U. O. Mchepange et al.
Family history and precipitating factors
Thirty-eight patients (5.5%) had a family history of
vitiligo. The frequencies of the first-, second- and mul-
tiple degree relatives are shown in Table II. Twenty-six
patients (3.8%) had other autoimmune diseases, with
hyperthyroidism (22.2%), rheumatoid arthritis (18.5%)
and alopecia areata (14.8%) being the most common.
Of the 249 cases reported, 8.0% (n = 20) had a rash
prior to vitiligo onset and 23.3% (n = 58) had vitiligo at
a site of significant physical trauma or operation either
prior to the onset of the disease or during the course of
the disease (Koebner’s phenomenon). 8.4% (n = 21) had
vitiligo around a naevus (halo phenomenon).
Premature hair greying and leukotrichia
Sixty-six patients (26.5%) of the 249 cases had prema-
ture hair greying, with 97.0% of those showing greying
of scalp hair. The remainder of the patients (3.0%)
showed greying of other body hairs, such as eyebrows,
eyelashes, beard and moustache.
The mean onset age of premature hair greying was
15.50 ± 5.41 years (range 3–24, median 17). Male sub-
jects slightly outnumbered the females (41 males, 25
females), but this difference was not statistically signi-
ficant (p = 0.455). Most of the patients with premature
hair greying were those with vitiligo vulgaris (n = 33),
followed by focal (n = 24), acrofacial (n = 5), mixed
(n = 3) and universal (n = 1) vitiligo.
This distribution mirrors the distribution of vitiligo
types in general.
Forty patients (16.1%) of the 249 cases reported one
or more other family members with premature hair
greying. The odds of having a family history of pre-
mature hair greying were more than four times greater
among those who had premature hair greying than for
those who did not, and the difference was statistically
significant (OR = 4.028, χ2 = 16.530, p < 0.001). Our
results show that vitiligo patients with a family history
of premature greying are more likely to develop prema-
ture greying themselves. However, no comparison with
the general population was made, and, due to greater
awareness of pigmentary phenomena among individuals
who themselves have vitiligo and/or premature greying,
it remains unclear whether this represents a true familial
tendency of premature greying among these patients or
biased reporting of relatives with premature greying
among these patients.
Seventy-three (29.3%) cases reported white hairs on
vitiliginous sites (vitiliginous leukotrichia). There was
no statistical significance in showing vitiliginous leu-
kotrichia between male and female subjects (38 males,
35 females, p = 0.208). Most patients who showed viti-
liginous leukotrichia were those with vitiligo vulgaris
(n = 36), followed by focal (n = 26), acrofacial (n = 5),
mixed (n = 3), and universal (n = 3) vitiligo. Again, this
distribution mirrors the distribution of vitiligo types in
general.
We found a significant difference in vitiliginous
leukotrichia between patients in the progressive stage
(n = 51) and those in the stable stage (n = 20, p < 0.01).
The difference in vitiliginous leukotrichia between pro-
gressive and regressive stage (n = 2, p = 0.095), or stable
(n = 20) and regressive stage (n = 2, p = 0.571) were not
statistically significant. Vitiliginous leukotrichia was not
associated with disease duration (data not shown).
The odds of having premature hair greying were more
than four times greater for those who had vitiliginous
leukotrichia than for those who did not (OR = 4.735,
χ2 = 27.582, p < 0.001).
The odds of having a rash prior to the onset of viti-
ligo were more than three times greater for those who
had vitiliginous leukotrichia than for those who did not
(OR = 3.292, χ2 = 6.922, p < 0.05).
DISCUSSION
Most of the clinical results obtained in this study are
similar to those reported in other parts of China and
elsewhere in the world. Vitiligo vulgaris was the most
common type in our study, and this agrees well with
the results obtained in Tunisia, India, Turkey and other
parts of China (9–11, 14). Lack of sexual preponde-
rance has also been reported in India, Tunisia, Turkey,
Denmark and other parts of China (10–12, 14, 15).
While our study shows the back to be the most com-
mon site of involvement at onset, other studies have
shown the face, head and neck, lower limbs and upper
limbs to be the most common sites of involvement at
onset (9–11, 14). Our results show a family history of
vitiligo in 5.5% of patients, lower than those reported
in other studies (11.1–30%) (9, 10, 12, 16). Vitiliginous
leukotrichia has been reported worldwide at a range of
9–47.3% (9–11, 17). We observed leukotrichia in 29.3%
of subjects, which falls within this range.
Reports on association of vitiligo with other autoim-
mune diseases vary widely depending on the patient
populations studied. Age of patients at the time of study,
the number of autoimmune diseases analysed, as well
as the patient’s ability to distinguish different forms of
autoimmune diseases also affect the accuracy of the
frequencies reported. Association of vitiligo with other
Table II. Frequencies of first-, second- and multiple-degree relatives
with vitiligo in North-eastern China
Relative
Frequency
n (%)
First-degree relative
Second-degree relative
Multiple-degree (first- and second-degree) relatives
Total
17 (44.7)
16 (42.1)
5 (13.2)
38 (100)
Acta Derm Venereol 90

Page 4

139
Vitiligo in North-eastern China
autoimmune diseases has been reported at frequencies
ranging from 4.76% to 7.6% in China in both adult and
childhood vitiligo (12, other references in Chinese).
Frequencies as low as 1.3% in childhood vitiligo, and
up to 43% in a Romanian population isolate have been
reported elsewhere in the world (18, 19). Our results
show low frequency (3.8%) of autoimmune diseases in
this population, though we cannot rule out the possibility
of under-reporting.
Despite the possible confounding bias from race, we
included both Han and non-Han Chinese in our study in
order to construct a representative model of this disease
based on geographical locality rather than race. The Han
ethnic group comprises more than 90% of the Chinese
population, and this was reflected in our study in which
93.8% of patients belonged to this group.
Our study found significant association between mu-
cosal and acrofacial forms of vitiligo, suggesting that
mucosal vitiligo may be a form of acrofacial vitiligo.
We also bring to the attention of dermatologists the
need for a universal definition of premature hair greying
with consideration of both onset and rate of progression
of hair greying. There is no current universal definition
of premature hair greying. Rosen et al. (7) defined
premature hair greying as hair turning more than 50%
grey before age 40 years. In another study, Orr-Walker
et al. (8) defined premature hair greying, a priori, as
the majority (> 70%) hair greying before age 40 years.
According to other authors, hair is said to grey prema-
turely if it occurs before age 20 years in whites, before
25 in Asians, and before 30 in Africans (6). The average
age of onset of hair greying is mid-30s for Caucasians,
late-30s for Asians and mid-40s for Africans; and a
simple rule of thumb suggests that by 50 years of age,
50% of people have 50% grey hair (Keough & Walsh,
1965) (6).
Our definition of premature hair greying was establis-
hed for the purpose of this study only, bearing in mind
that both onset and rate of progression are important in
defining hair greying. However, though we included a
self-report that the subject’s hair had turned more than
50% grey before age 40 years in the definition, all sub-
jects that reported premature hair greying did so due to
meeting the first part of our definition (i.e. they had hair
greying before age 25 years).
There are a few shortcomings in our definition. Hair
greying before age 25 years lacks visible parameters
required to make it comparable to self-report that hair
had turned more than 50% grey before age 40 years.
Previous studies have not quantified the extent of in-
volvement of hair greying before age 25 years for it
to be regarded as premature. Although we excluded
the occasional few grey hairs that develop in children,
these could represent a true onset of greying and thus
could have a significant impact on the interpretation of
our results.
We found that vitiligo patients with a family history of
premature hair greying are more likely to show prema-
ture hair greying than those without a family history of
premature hair greying. However, while premature hair
greying is believed to tend to run in families, we found
little published evidence to support this or to document
its inheritance in the general population, thus limiting
the opportunity to compare our data from vitiligo pa-
tients with analogous data from controls.
ACKNOWLEDGEMENTS
We are indebted to our colleagues and friends from No. 1 and
No. 2 hospitals of China Medical University, No. 7 People’s
Hospital, the General Hospital of Shenyang Military Command,
the First Hospital of Beihua University, the Second Hospital of
Jilin University, and Liaoning University of Traditional Chinese
Medicine for their co-operation and support. We wish to thank
Professor Richard A. Spritz of University of Colorado Denver
for his critical review of the manuscript.
This work was supported in part by the Programmes of
Changjiang Scholars and Innovative Teams of the Ministry of
Education of China (IRT0760).
The sponsors had no role in the design and conduct of the
study; in the collection, analysis, and interpretation of data; or
in the preparation, review, or approval of the manuscript.
The authors declare no conflict of interest.
REFERENCES
Njoo MD, Westerhof W. Vitiligo. Pathogenesis and treat-1.
ment. Am J Clin Dermatol 2001; 2: 167–181.
Ruiz-Argüelles A, Brito GJ, Reyes-Izquierdo P, Pérez-2.
Romano B, Sánchez-Sosa S. Apoptosis of melanocytes in
vitiligo results from antibody penetration. J Autoimmun
2007; 29: 281–286.
Nath SK, Majumder PP, Nordlund JJ. Genetic epidemiology 3.
of vitiligo: multilocus recessivity cross-validated. Am J
Hum Genet 1994; 55: 981–990.
Orecchia GE: Neural pathogenesis. In Vitiligo. Hann SK, 4.
Nordlund JJ, editors. London: Blackwell Science; 2000,
p. 142.
Rezaei N, Gavalas NG, Weetman AP, Kemp EH. Autoim- 5.
munity as an aetiological factor in vitiligo. J Eur Acad
Dermatol Venereol 2007; 21: 865–876.
Tobin DJ, Paus R. Graying: gerontobiology of the hair fol-6.
licle pigmentary unit. Exp Gerontol 2001; 36: 29–54.
Rosen CJ, Holick MF, Millard PS. Premature graying of hair 7.
is a risk marker for osteopenia. J Clin Endocrinol Metab
1994; 79: 854–857.
Orr-Walker BJ, Evans MC, Ames RW, Clearwater JM, Reid 8.
IR. Premature hair graying and bone mineral density. J Clin
Endocrinol Metab 1997; 82: 3580–3583.
Dogra S, Parsad D, Handa S, Kanwar AJ. Late onset vi-9.
tiligo: a study of 182 patients. Int J Dermatol 2005; 44:
193–196.
Handa S, Kaur I. Vitiligo: clinical findings in 1436 patients. 10.
J Dermatol 1999; 26: 653–657.
Akrem J, Baroudi A, Aichi T, Houch F, Hamdaoui MH. 11.
Profile of vitiligo in the south of Tunisia. Int J Dermatol
2008; 47: 670–674.
Hu Z, Liu JB, Ma SS, Yang S, Zhang XJ. Profile of child- 12.
hood vitiligo in China: an analysis of 541 patients. Pediatr
Acta Derm Venereol 90

Page 5

140
U. O. Mchepange et al.
Dermatol 2006; 23: 114–116.
Liu JB, Li M, Yang S, Gui JP, Wang HY, Du WH, et al.
Clinical profiles of vitiligo in China: an analysis of 3742
patients. Clin Exp Dermatol 2005; 30: 327–331.
Arýcan O, Koç K, Ersoy L. Clinical characteristics in 113
Turkish vitiligo patients. Acta Dermatovenerol Alp Pano-
nica Adriat 2008; 17: 129–132.
Howitz J, Brodthagen H, Schwartz M, Thomsen K. Pre-
valence of vitiligo: epidemiological survey on the Isle of
Bornholm, Denmark. Arch Dermatol 1977; 113: 47–52.
Odom RB, James WD, Berger TG, editors. Andrews’
diseases of the skin: clinical dermatology, ninth edition.
13.
14.
15.
16.
Philadelphia: WB Sanders; 2000.
Ortonne JP, Bahadoran P, Fitzpatrick TB, Mosher DB, Hori
Y. Hypomelanosis and hypermelanosis. In: Freedman IM,
Eisen AZ, Wolff K, Austen KF, Goldsmith LA, Katz SI,
editors. Fitzpatrick’s dermatology in general medicine. New
York: McGraw Hill; 2003, p. 836–881.
Handa S, Dogra S. Epidemiology of childhood vitiligo: a
study of 625 patients from north India. Pediatr Dermatol
2003; 20: 207–210.
Birlea SA, Fain PR, Spritz RA. A Romanian population
isolate with high frequency of vitiligo and associated au-
toimmune diseases. Arch Dermatol 2008; 144: 310–316.
17.
18.
19.
Acta Derm Venereol 90