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Vitiligo: Symptoms, Pathogenesis and Treatment

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INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY Yol. 27, no. 4, 485-489(2014)

EDITORIAL
VITILIGO: SYMPTOMS" PATHOGENESIS AND TREATMENT

E. GHAFOURIANI, S. GHAFOURIAN" N. SADEGHIFARD2,R. MOHEBI2,

Y. SHOKOOITTNI3.S. NEZAMOLESLAMII ANdR.A. HAMAT4

Istudent ResearchCommittee,Kermanshah University of Medical Sciences,Kermanshah,

Iran; 2Clinical Microbiology ResearchCenter llam (Jniversity of Medical Sciences,Ilam, Iran;
3Departmentof Pharmacognosyand Biotechnology, School of Pharmacy, Kermanshah University
of Medical Sciences,Kermanshah,Iran; aDepartmentof Medical Microbiolog,t and Parasitology,
Faculty of Medicine and Health Sciences,Universiti Putra Malaysia, Serdang,Malaysia

Received August 23, 2014 - Accepted September 22, 2014

Vitiligo is an acquired cutaneous disorder of pigmentation, with an incidence of 0,5oh to 2oh

worldwide. There are three major hypotheses for the pathogenesis of vitiligo that are not exclusive
of each other: biochemicaVcytotoxic, neural and autoimmune. Recent data provide strong evidence
supporting an autoimmune pathogenesis of vitiligo. As vitiligo can have a major effect on quality
of life, treatment can be considered and should preferably begin early when then disease is active.
Current treatment modalities are directed towards stopping progression of the diseaseand achieving
repigmentation. Therapies include corticosteroids,topical immunomodulatorso photo(chemo)therapy,
surgery,combination therapiesand depigmentationof normally pigmented skin.It seemsthat traditional
Chinese medicine could be more effective than the current treatment for vitligo.

Vitiligo is known as a condition in which caseshair follicle melanocytes.Segmentalvitiligo is an

depigmentationof the part of skin occurs (Fig. 1).
Loss of the functionality of melanocytesis responsible
for vitiligo but the real causeof vitiligo is unknown.
However, some conditions including autoimmune,
genetic,neural,viral infectionsandoxidativestresscould
havean importantrole in vitiligo (1). The prevalenceof
vitili go i s less than2o/oworldwid e (2) . Vitili go i s divided
into two types: Chemical and idiopathic. The majority
of vitiligo belongs to the idiopathic type. ln vitiligo
the hair and oral mucosa may also be depigmented.
Generalizedvitiligo or non-segmentalvitiligo (NSV)
are charactenzedby white patches,often symmetrical,
that usually increasein sizewith time, correspondingto
a substantialloss of functioning epidermaland in some
acquired chronic pigmentation disordeg charactenzed
by white patcheswith a unilateral distribution that may
totally or partially match a dermatome(3).
Symptoms
The most important symptomof vitiligo known is
the depigmentationof patchesof skin. Initially, the
patchesare small but they will be enlargedover time.
The skin lesionsaredominantly observedon the face,
hands and wrists. Often patients who are suffering
from this diseasealso suffer from depression(4).
Pathogenesis
Although the cause of vitligo is unknown, there

Key words: vitiligo, Chinese medicine, treatment

Mailing address:Associate Prof. Dr RukmanAwang Hamat,

Department of Medical Microbiology and Parasitology, 0394-6320(2014)
Faculty of Medicine and Health Sciences, Copyright O by BIOLIFE, s.a.s.
Universiti Putra Malaysia. This publication and/or article is for individual use only and may not be further
reproduced without written permission from the copyright holder.
43 400 Serdang,Malaysia
Unauthorized reproduction may result in financial and other penalties
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486 E. GHAFOURIAN
are three hypothesesfor its pathogenesisincluding
biochemicall cytotoxic, neural and autoimmune: the
biochemical/cytotoxic hypothesis emphasizesthat
vitiligo occurs when the melanocyte is killed by
cytotoxic precursorsto melanin synthesis;the neural
hypothesis is based on nerve injury development
with effected sites that leads to segmentalvitiligo
with neurons that interact with melanocytes and
releasemelanocytotoxicsubstrates;the autoimmune
hypothesisis based on genetic data which are more
associatedto autoimmunediseases(5).
Although these three theories are sufficient to
explain the mechanismsof vitiligo, the convergence
theoryis thatstress,accumulationoftoxic compounds,
infection, autoimmunity, mutations, altered cellular
environment and impaired melanocyte migration
and proliferation can all contribute in varying
proportionsto the etiopathogenesisof vitiligo (6).
Some evidence emphasizesthat vitiligo occurs
through autoimmunity. In a study where the lesion,
perilesional, and non-lesional skin biopsies from
patients with vitiligo were comparedwith immune
infiltrates found in the skin of normal healthy
donors and relevant diseasecontrols a major role
was observedfor skin-homing T cells in the death
of melanocytes seen in vitiligo (7). The family
history of vitiligo in 20oAto 30oAof patientsmakes
a chromatic role for genetic factors (8). However,
there is not sufficient datato support the exact cause
of vitiliso.
TREATMENT OF VITILIGO
Vitiligo is a skin condition characterizedbywhite
patches (hence, its alternative name, leukoderma;
leuko : white; derma : skin). These skin patches
are missing the skin pigment melanin; in most cases,
the condition is triggered by sunburn. Normally,
excessivesun exposurefirst causesskin reddening,
followed by peeling of the outer skin layers, and
formation of darker skin in the exposed area
("tanned" skin). However, in some cases,a reaction
occurs in which the melanin production is blocked
and the skin losesits color. The patchesof white are
usually at the site of the burn, but it is also possible
for additional patchesto begin appearingelsewhere.
Genetic factors are believed to contribute to the
susceptibility towards vitiligo, and the condition
ETAL.
might be triggered by conditions other than sunburn,
such as viral infections or physical trauma to the
skin. The disorder appearsto have an autoimmune
characteristic, in which melanocytes (melanin
producing cells) arc attackedand destroyed.Vitiligo
usually first appearsby the age of 20, though it can
begin later.
There are a number of treatments for vitiligo
with the best evidence for applied steroids and the
combinationof ultraviolet light in combinationwith
creams(9). Due to the higher risks of skin cancer,the
NHS suggestsphototherapyonly be used if primary
treatmentsare ineffective (10).
Phototherapy
Exposing the skin to UVB light from UVB
lamps is the most common treatment for vitiligo.
The treatment can be carried out at home with a
domestic UVB lamp or in a clinic. It is important
to control the exposuretime so that the skin does
not burn from overexposure. Treatment can take
a few weeks if the spots are on the neck and face
and if they have existed not more than 3 years. If
the spots are on the hands and legs and have been
there for more than3 years,it can take a few months.
In a clinic the treatmentsare carried ofi 2-3 times
a week, and at home every day, which makes the
home treatment more effective. Spots on a large
area of the body may require full body treatment in
a clinic or hospital. Both UVB broadbandand UVB
narrowbandlamps can be used(lI,l2). There is no
treatment that totally repigments the skin. Adding a
psoralen,a photosensitizer,or an immunomodulant
(13) that increasesthe effect of the UV light can aid
in partial repigmentation.
A 1997 report suggeststhat combining vitamin
B,, and folic acid supplementswith sun exposure
causedrepigmentationin 52o/oof cases(14).
Ultraviolet light (UVA) treatment is normally
carried out in a hospital clinic. Psoralen and
ultraviolet A light (PUVA) treatment involves
taking a drug that increasesthe skin's sensitivity to
ultraviolet light, then exposingthe skin to high doses
of UVA light. Treatmentis requiredtwice a week for
6-12 months or longer. Becauseof the high doses
of UVA and psoralen,PUVA may causeside effects
suchas sunburn-typereactionsor skin freckling (10).
Narrowband ultraviolet B (UVB) phototherapy is
 Int. J. Immunopathol. Pharmacol.
now used more commonly than PUVA as it is less
damaging to the skin. As with PUVA, treatment is
carried out twice weekly in a clinic or every day at
home,and thereis no needto usepsoralen(10).
Immune mediators
Tentativeevidencesupportsa role for tacrolimus
(15) There is short-termevidencefor pimecrolimus
but long-termdatais missing(16).
Skin camouflage
In mild cases,vitiligo patchescan be hiddenwith
makeup or other cosmetic camouflage solutions.
If the affectedperson is pale-skinned,the patches
can be made less visible by avoiding tanning of the
affectedskin (17).
De-pigmenting
In cases of extensive vitiligo the option to de-
pigment the unaffected skin with topical drugs like
monobenzone)mequinol, or hydroquinone may be
consideredto render the skin an even colour. The
removal of all the skin pigment with monobenzoneis
pennanentand vigorous. Sun-safetymust be adhered
to for life to avoid severesunburn and melanomas.
Depigmentationtakesabout ayear to complete(10).
Transplanting melanocytes
In October1992,a scientificreportwas published
of successfullytransplantingmelanocytesto vitiligo
affected areas, effectively repigmenting the region
(18). The procedureinvolved taking a thin layer of
Fig. 1. l{on-segmentalvitiligo of the hand.
487
pigmented skin from the patient's gluteal region.
Melanocytes were then separatedout to a cellular
suspensionthat was expandedin culture. The area
to be treatedwas then denudedwith a dermabrader
and the melanocytesgraft applied. Between 70 and
85 percentof patientsexperiencednearly complete
repigmentation of their skin. The longevity of the
repigmentationdiffered from personto person(19).
Chinesemedicinefor treatmentof vitiligo
PUVA therapy is not very satisfactoryexcept for
small patches;while somepeoplerespondwell, the
majority attarnonly parttal pigmentation and are not
happywith the results(20). The therapyis disruptive,
in that it may need to be applied repeatedly (with
individual office visits) for many weeks. Over-the-
counter,self-appliedpsoralenshavebeendeveloped
as an alternative;while more convenient,this does
not necessarily improve the outcome. The PUVA
method is most effective when vitiligo is limited
to only one or two clearly definedpatches,and less
useful when there are multiple patches.
Chinese medicine has been applied to treat
vitiligo, and many of the treatments involve
combinedtopical and internal use of psoraleaseed
extract, rich in psoralens.As with PUVA, there is
limited successwith this method. However, herbal
formul asaimed at tr e ating autoimmune di sordersand
those aimed at systemicimprovements(especially
in the blood components)may have a better effect.
Reports of successfultreatment appear from time
to time in the Chinesemedical literature and some
clinics advertise their treatments with before and
after pictures of successfulcases.Complex patent
herbalmedicinesand topical applicationsfor vitiligo
- aside from psoraleaextracts- have been produced
by severalfactories. Some of the Chinesetherapies
offered are depicted in the following pages, based
on their presentationvia websites, with editing to
improve their clarrty
The main therapeutic principle for treating
vitiligo is nourishing the kidney, promoting blood
circulation, and dispelling pathogenic wind. There
are three alternative recipes for internal use and a
topical therapy (21).
Compoundtablet of Tribulus: the main herbs are
tribulus, spirodela, ho-shou-wu, xanthium, tang-
kuei, scorpion, carthamus,and cnidium. The herbs
 E. GHAFOURIAN ETAL.
488
are ground into fine powder to make tablets. Take 10
grams are taken, three times a day.
Recipe by physician Yang Hengyu: the main
herbs are astragalus,tang-kuei, peony, red peony,
raw rehmannia, cooked rehmannia, ho-shou-wu,
lycium, cuscuta,cnidium, tribulus, angeltca,persica,
and carthamus.The herbs are to be decoctedin water
for oral administration.
Shou WuDecoction: the main herbs are ho-shou-
wu, black sesameseed, peony, red peony, albizzia,
raw rehmannia, cooked rehmannia, prunella,
astragalusseed, gentiana,carthamus,polygala, tang-
kuei. salvia.The herbsare to be decoctedin water for
oral administration.
External T4eatment: Grind 5 grams each of
realgar, sulfur and typhonium tuber, 2 grams of
litharge, 15 grams of cnidium fruit and 0.5 grams of
calomel into fine powder and mix with vinegar for
application on the affectedpart, twice a day, or use
ginger to dip powder to rub the affected part, twice
a day.The patient must be treatedthis way for more
than 3 months.
The pathogenicfactorsof vitiligo aremainly: heat
in the blood or bodily heat; invasion by exogenous
wind or damp, which invade the skin resulting in
disorderof the circulation ofblood at the surface;and
blockageof the channelsand vessels(thus,the blood
cannot nourish the skin leading to qi-stagnationand
hair-orifices blocked). Becausethe hair-orifices are
blocked, the affectedskin looks glossy.
Vitiligo usually developsrapidly in the spring and
summer.In some casesa feeling of itching precedes
expansion of the white patches. If a patient's
constitution is worsenedby bad morale or by some
exogenous factors, the pathological condition
advances continuously. Quite a few patients miss
the best time for treatment of the disease,when it
first appears, trusting that it will simply resolve
spontaneously; once the arca affected becomes
bigger than the original spots, the time required to
cure the diseasewill be longer (22).
It is better to treat the ailment completely; one
should rely on traditional Chinese medicine to
regulate the qi and blood, clear away the heat,
activate the blood circulation, and dredge the
channelsand vesselsin order to support the healthy
energy and strengthenbody resistance.A series of
vitiligo-resolving medicines are manufacturedwith
genuineChineseherbs,which arenon-toxic, produce
no side effects,and require arelatively short term of
treatmentto attain a rapid and permanenteffect. The
herb preparations are applied topically and taken
orally in convenient form; as a result of treatment,
there is rarely a recuffenceof vitiligo and there is a
high rate of improvement,reaching 98%oand a cure
rate over 80%. Vitiligo is an obstinate ailment, so
the treatment time period might be long; howeveq
the diseaseis not incurable. During the course of
treatment,one should follow closely the instructions
for using the herbs, and maintain a good mental
state,to get the desiredresults.Personswith vitiligo
should avoid direct sun exposure and prolonged
living in a damp environment,avoid air conditioning
when sweating, maintain a regular living habit,
and avoid some potentially initating foods such as
shrimp, crab,lamb, chili and other spices.If white
patchesbegin to appear,they should be treated as
early as possible.
Modern pharmacological research has
demonstrated that cinnamon twig can dilate blood
vessels and enhance microcirculation. Astragalus,
ho-shou-wu,lycium, and cordycepscan regulatethe
body immune function and maintain homeostasis.
All of the ingredientswhen used in combinationcan
nourish the liver andkidney, invigorate qi andnourish
blood, dispel pathological qi and qi stagnation,and
remove wetness, invigorate blood, activate blood
circulation and dissipateblood stasis,clear channels
and collaterals and remove patches. This internal
therapy is the treatment of the primary aspectof the
disease.The topical herbal preparationsare made
by soaking angelica and cinnamon bark in ethanol.
Angelica canpromotemelanocyteregenerationwhile
cinnamonbark is acid-sweetand warming, so it can
dissipateblood stasisand promoteblood circulation;
it can dilate peripheral blood vessels and,increase
local blood flow when applied topically. This topical
treatmentwill activatethe melanocytes.andtreat the
external aspectof the disease.When the above oral
and topical therapiesare used in combination, both
the principal and secondarysymptoms are treated at
the sametime.After 3 monthstreatmentwith Chinese
herbal medicine, the treatmentcan be supplemented
with epidermal autografting to increase the number
of melanocytesin the lesion areas,promote healing
of the white patches, and shorten the treatment
 Int. J. Immunopathol. Pharmacol.
duration while increasingthe cure rate.
CONCLUSION
Many studieshave been performed to determine
which treatment is the best for vitiligo. Since there 12. Philip D, Aurel I, Anne D, KathleenH. Treatment
is no consensuson the pathogenesisof vitiligo, a
treatmentto completely cure vitiligo does not exist.
More randomized controlled trials on the treatment
of vitiligo are necessary.
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