INVITED ARTICLE

Metabolic syndrome in vitiligo

Aldona Pietrzak*, Joanna Bartosin ska*, Jana Hercogov,
Torello M. Lotti & Grazyna Chodorowska*
*Department of Dermatology, Venereology and Paediatric Dermatology,
Medical University, Lublin, Poland, Department of Dermatology, 2nd
Medical Faculty, Charles University Prague, Bulovka University Hospital,
Prague, Czech Republic and University of Rome G. Marconi, Rome, Italy
ABSTRACT: Vitiligo is an acquired, depigmenting skin disease with still unclear, multifactorial etio-
pathogenesis. However, there is growing evidence that vitiligo affects not only the skin but it may also
be connected with metabolic abnormalities, including glucose intolerance and lipid abnormalities, all
of which conrms the systemic nature of the disease. Recently, it has been shown that melanocytes,
especially those found in the adipose tissue, due to their ability to decrease inammation and oxidative
damage, are capable of preventing the metabolic syndrome. The article presents updated knowledge on
potential metabolic disturbances in vitiligo.
KEYWORDS: metabolic abnormalities, oxidative stress, vitiligo
Introduction
The metabolic syndrome, which is a combination
of abdominal obesity, dyslipidemia, glucose intol-
erance, diabetes mellitus, and hypertension, is a
well-established condition in some inammatory
skin diseases, including psoriasis (1). Although the
pathogenesis of the metabolic syndrome coincides
inmanyrespects withthepathogenesis of psoriasis,
this relationship still awaits investigationinvitiligo.
Vitiligo, an acquired depigmenting skin disease
of unknown origin and multifactorial etiopatho-
genesis, has recently been seen as an afiction that
does not merely affect the skin, but it seems to have
a potential to trigger the development of general-
ized abnormalities of the systemic nature. There-
fore, at present, researchers are making an attempt
to elucidate the issue of the metabolic syndrome in
vitiligo. If they prove the existence of metabolic
disturbances invitiligo, the development of athero-
sclerosis and other cardiovascular diseases could
be expected, which would change the future man-
agement of vitiligo patients.
The complex vitiligo pathogenesis, in which
genetic, immunological, autoimmunological, cyto-
toxic, neuronal, and inammatory factors are
involved, might explain a wide spectrum of its sys-
temic manifestations. It is well known, however,
that in vitiligo autoantibodies production results
in the development of autoimmunological comor-
bidities, such as alopecia areata, autoimmune
thyroid disease, Addisons disease, pernicious
anemia, type I diabetes mellitus, and myasthenia
gravis (2,3). Furthermore, the proinammatory
cytokines (tumor necrosis factor, interleukin 1, and
interleukin 6) and other inammatory factors
engaged in vitiligo are known to be involved in
evoking insulin resistance as well as other meta-
bolic complications and atherosclerosis (4). Even
though few reports have provided information on
the metabolic disturbances in vitiligo, so far, a
recent study has found that insulin resistance as
well as some lipid prole disturbances may occur
in vitiligo patients (5). Karadag et al. (5) found that
Address correspondence and reprint requests to: Aldona
Pietrzak, MD, PhD, Assistant Professor, Department of
Dermatology, Venereology and Paediatric Dermatology,
Medical University, 13 Radziwillowska St., 20-080 Lublin,
Poland, or email: aldonkapietrzak@o2.pl.
S41
Dermatologic Therapy, Vol. 25, 2012, S41S43
Printed in the United States All rights reserved
2012 Wiley Periodicals, Inc.
DERMATOLOGIC THERAPY
ISSN 1396-0296
in the vitiligo patients they studied, the high
density lipoprotein (HDL)-cholesterol concentra-
tion was decreased and the low density lipoprotein
(LDL)/HDL ratio was increased, which turned out
to be statistically signicant. The same study also
reported that even in nondiabetic vitiligo patients,
a higher insulin resistance as well as higher insulin
and C-peptide levels were observed in comparison
with the control group.
Investigation of the lipid disturbances in the
vitiligo children, which was conducted in our
department, has revealed decreased levels of
HDL-cholesterol as well as increased triglyceride
concentrations and a tendency for increased LDL-
cholesterol levels and decreased HDL phospho-
lipid concentrations in the studied group of vitiligo
girls (6). In another unpublished study, our lipid
prole analysis showed a signicantly lower
HDL-cholesterol concentration and a signicantly
higher LDL-cholesterol concentration in the
studied vitiligo children in comparison with the
healthy control group. Also, the value of the LDL/
HDL ratio was signicantly higher in the vitiligo
patients in relation to the healthy individuals.
All our ndings provide evidence that lipid dis-
turbances may develop even in young vitiligo
patients, which would stand in contradiction to the
view of Rodrguez-Martn et al. (7) who claimed
otherwise. In their recent study, comprising 105
active nonsegmental vitiligo patients aged 1485
years, Rodrguez-Martn et al. (7) found out that
the studied patients presented a better lipid prole,
with higher levels of HDL and lower triglyceride, in
comparison with the control group. Even though in
their opinion vitiligo patients might be at a lower
cardiovascular risk because of the controversial
choice of the studied subjects (i.e., their age, sex),
the results of Rodrguez-Martnet al. are debatable.
However, the latest study of Karadag et al. (8) has
revealed that the levels of homocysteine, known
to inhibit tyrosinase, an enzyme participating in
melanine synthesis, and increase the cardiovascu-
lar risk, were higher in the group of vitiligo patients
in comparison with the controls. This nding
seems to suggest that homocystine, among other
contributing factors, may be involved in the devel-
opment of the metabolic disturbances in vitiligo
patients. Similarly, Silverberg and Silverberg (9)
found that vitiligo patients have higher homocys-
teine and lower vitamin B12 serumconcentrations,
which correlates with body surface area affected
with the disease, number of body parts involved,
and bilaterality of the skin lesions.
The role of melanocytes is another factor worth
investigating, especially in light of the reports that
speculate and hypothesize on the role of melanin
in obesity-related pathologies, thus, also in the
metabolic syndrome. Melanocytes are known to
be found not only in the skin and hair follicles but
also in the retinal pigment epithelium cells as well
as in some cells of the inner ear and other parts
of the central nervous system. Interestingly, quite
recently, melanocytes have been identied in the
adipose tissue, where they are believed to take
part in anti-inammatory reactions as well as
in the reduction or binding of reactive oxygen
species (ROS), such as singlet oxygen, hydroxyl
radicals, and superoxide anions, acting as scaven-
gers of free radicals and other oxidative species
(4,10,11). This nding seems to be in agreement
with the observation that melanogenesis is higher
in the obese humans in comparison with the indi-
viduals presenting the correct body mass index
values (11). It is so because in the obese the serum
levels of the endogenous melanogenic peptide
a-melanocyte stimulating hormone (a-MSH),
which binds to the melanocortin 1 receptor
(MC1R) on human adipocytes and triggers mel-
anogenesis in them, are higher (12,13). As the oxi-
dative stress plays a vital role in the pathogenesis
of both the metabolic syndrome and the vitiligo, it
seems plausible that a decreased number of mel-
anocytes as well as decreased melanogenesis in
the adipose tissue might contribute to the meta-
bolic disturbances in vitiligo patients. Hence, the
aforementioned metabolic disturbances in vitiligo
seem to result from an increased production of
the ROS. Excessive ROS is known to be respon-
sible for lipid peroxidation, protein oxidation, and
oxidative DNA damage (14). Therefore, in order to
prevent the development of the metabolic syn-
drome, Page et al. (4) suggested that agonists of
melanin production, such as a-MSH or its syn-
thetic analogs, should be tested as potential
therapeutic agents. Furthermore, a case report
presented by Nol et al. (15) indicates statins as
immune-modulating medications, which not only
improve lipid prole but also may play a role in
the treatment of vitiligo patients.
To sum up, the involvement of the metabolic
syndrome in vitiligo requires further investigation
for only a clear and unambiguous identication of
a pathogenic relationship between them will be of
clinical importance.
Conict of interest
None.
Pietrzak et al.
S42
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Metabolic syndrome in vitiligo
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