Current and emerging treatments

for vitiligo
Michelle Rodrigues, MBBS(Hons), FACD,a,b Khaled Ez
Ezzedine, MD, PhD,c,d Iltefat Hamzavi, MD,e
f  g

 Amit G.
Victoria, Pandya, Creteil,
Australia; MD, and John E.
France; Harris,Michigan;
Detroit, MD, PhD, Dallas,
on behalf of the
Texas; andVitiligo Working
Worcester, Group
Massachusetts

Learning objectives
 After completing this learning activity, participants should be able to choose an optimal approach to management of all patients with vitiligo; list the risks associated with treatment for
 vitiligo; and discuss emerging treatment options for vitiligo.

Disclosure
Editors
The editors involved with this CME activi
activity
ty and all content validation/peer
validation/peer reviewers of the journal-based
journal-based CME activity
activity have reported no relevant
relevant financial relationships
relationships with
commercial interest(s).

 Authors
Theauthorss involvedwiththisjourn
Theauthor involvedwiththisjournal-b
al-basedCMEactivi
asedCMEactivityotherthanDr
tyotherthanDr Harrishavereport
Harrishavereportedno
edno rele
relevantfinanc
vantfinancialrelat
ialrelations
ionshipswithcomme
hipswithcommercia
rcialinteres
linterest(s)
t(s).. DrHarrris
DrHarrris hasservedonadviso
hasservedonadvisory 
ry 
boards,as a consultant,
consultant, oras principleinvestigatoron researchagreementswith Pfizer,
Pfizer, AbbVie,Genzyme/Sanofi
AbbVie,Genzyme/Sanofi,, ConcertPharmaceuticals,
ConcertPharmaceuticals, Stiefel/GSK,
Stiefel/GSK, Mitsubish
Mitsubishii TanabePharma,Novartis,
 Aclaris Therapeutics,
Therapeutics, The Expert Institu
Institute,
te, Celgene, Biologics
Biologics MD, and Dermira. Dr Harris’ relevant relati
relationship
onship with Pfizer was resolv
resolved
ed by nonconflicted reviewers
reviewers and editors.
Planners
The planners involved with this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). The editorial and education staff involved
 with this journal-based CME activity have reported no relevant financial relationships with commercial interest(s).

Clinicians should be aware that vitiligo is not merely a cosmetic disease and that there are safe and effective
treatments available for vitiligo. It is important to recognize common and uncommon presentations and
those with active disease, as well as their implications for clinical management; these were discussed in the
first article in this continuing medical education series. Existing treatments include topical and systemic
immunosuppressants, phototherapy, and surgical techniques, which together may serve to halt disease
progression, stabilize depigmented lesions, and encourage repigmentation. We discuss how to optimize the
currently available treatments and highlight emerging treatments that may improve treatment efficacy in the
future. ( J Am Acad Dermatol 2017;77:17-29.)

Key words:  afamelanotide;
  afamelanotide; biologics; corticosteroids; excimer lamp; excimer laser; grafting; leukoderma;
methotrexate; narrowband ultraviolet light; phototherapy; pigmentation; tacrolimus; treatment; vitiligo.

MEDICAL TREATMENTS d  Topical tacrolimus 0.1% should be used

Key points tw
twic
ice
e da
dail
ily
y for
for aff
affec
ected
ted are
areas
as on th
the
e fa
face
ce
d Potent or ultrap
Potent ultrapotent
otent topica
topicall corticosteroi
corticosteroids
ds and intertriginous areas
admini
adm iniste
stered
red in a cyc
cyclic
lical
al fashion
fashion avo
avoids
ids d Narrowband ultraviolet B light phototherapy 
adverse effects ap
appea
pears
rs to be sa
safe
fe an
and
d eff
effec
ecti
tive
ve when 
when [5-10%

From the Department of Dermatology,a St. Vincent’s Hospital, The Conflicts of interest: See above.
Ski
Skin
n and CanCancer
cer Founda
Foundatio
tion
n Inc,
Inc, and The RoyRoyalal Childr
Children’
en’ss Accepted for publication November 6, 2016.
Hospital,b Victo
Victoria,
ria, Austr
Australia;
alia; Department
Department of Dermat ology,,c
Dermatology Reprints not available from the authors.
Henrii Mondo
Henr Mondorr Hospital,
Hospital, and EpiDe rmE,d Universite Paris-Est,
EpiDermE, Corres
Correspon
ponden
dence
ce to: Michel
Michelle
le Rodrig
Rodrigues
ues,, MBBS(Ho
MBBS(Hons)
ns),, FACD,
FACD,
Creteil,
Cret eil, Franc
France;
e; Departmen
Departmentt of DermaDermatolog y,e Hen
tology, Henry
ry Ford
Ford Department
Depar tment of Dermatolog
Dermatology, y, 41 Victoria
Victoria Parade,
Parade, Fitzroy, VIC
Hospital,
Hospi tal, Detro
Detroit;
it; Department
Department of DermaDermatolog y,f  Unive
tology, University
rsity of  E-mail:   [email protected]
3065, Australia. E-mail:  [email protected].
Texa
Texass Sout
Southw
hweseste
tern
rn Medi
Medicacall Cent
Center
er,, DaDall
llas
as;; and
and th the
e 0190-9622/$36.00
Departmen
Depar tmentt of Derma
Dermatolog y,g Unive
tology, University
rsity of Massac
Massachusett
husettss  2016 by the American Academy of Dermatology, Inc. Published
Medical School, Worcester. by Elsevier Inc. All rights reserved.
Supported
Suppor ted by the National Institute
Institute of Arthritis
Arthritis and Musculoskel-
Musculoskel- http://dx.doi.org/10.1016/j.jaad.2016.11.010
etal and Skin Diseases, part of the National Institutes of Health, Date of release: July 2017
under Award Numbers AR061437 and AR069114, and research Expiration date: July 2020
grants
gran ts from the Kawaja
Kawaja Vitil
Vitiligo
igo Resea
Research
rch Initia
Initiative,
tive, Vitiligo
Research
Resea rch Founda
Foundation,
tion, and Dermatolog
Dermatologyy Found
Foundatio
ationn Stief
Stiefel
el
Scholar Award (to Dr Harris).

17
 

18   Rodrigues
Rodrigues et
et al  J A M A CAD
CAD  D ERMATOL
JULY  2017
  2017

 body surface area is affected; focused  Topical calcineurin inhibitors (level II

narrowband
narrowb and ultrav
ultraviolet
iolet B ligh
lightt photo
phototherap
therapy,
y, evidence)
such as hand and foot units or excimer laser, In recently published guidelines, the European
is useful in localized disease Dermato
Derm atolog
logyy Forum
Forum groupgroup propose
proposed d twi
twice
ce daily 
daily 
d  Topical tacrolimus 0.1% used twice per week  topicall calcineurin
topica calcineurin inhibit
inhibitorsors   f o
orr head
head and
and neckneck
5
may help prevent relapse after repigmenta- lesions as a first-line approach. This recommenda-
tion is achieved tion is based on a combination of its efficac efficac y in these
1 sites and its favorable side effect profile. 6,7  W  Warnings
arnings
 Vitiligo is not a ‘‘cosmetic disease,’’ so treatment have been placed on the long-term use of tacrolimus
can and should be offered to patients. The optimal because of a theoretical long-term risk of cancer,
treatment of vitiligo will first depend on the subtype despite its repeatedly demonstrated safety. 8 Other
of the disease, percent of body surface area (BSA) than
tha n exposu
exposurere to medica
medically lly adm
admini iniste
stered
red phophoto-
to-
involved, effect on quality of life, and the perception
therapy
thera py or excimer
excimer laser,
laser, photoprotection
photoprotection should
of the patient concerning the risk to benefit ratio. For
be encouraged when using topical immunosuppres-
exampl
exa mple,e, in the sesegme
gmenta
ntall varian
variantt of vitili
vitiligo,
go, the si
sion.
on. When
When usin
using
g a cycl cyclic
ical
al regi
regimemen n for
for topi
topica
call
disease follows a predictable course, with a phase of  steroids outlined above, calcineurin inhibitors may 
rapid spreading and early hair follicle involvement be used
used on the ‘‘off
‘‘off’’’’ days
days to provid
provide e cons
consististent
ent
re
rest
stric
ricte
ted
d to th the
e afaffe
fecte
cted
d segm
segmen
entt lasti
lasting
ng 3 to tre
treatm
atment
ent wit
withou
houtt inc
increareasing
sing the risk risk of advers
adverse e
24 months. This is usually followed by complete events.
stabil
stabilizat
ization
ion.. The segme
segmental
ntal variant
variant is therefo
therefore re more
more
difficult to treat and requires early medical interven-
Phototherapy 
tion or a surgical approach late in the disease course.
There are 2 main indications for the use of whole-
 With all types of vitiligo, timing of treatment is an
important predict
predictor
or of success, with early disease body
([5-1 pho
photot
5-10%
0% tother
of herapy
BSAapy
BSA) ) andin rapidl
vitili
vitiligo:
rap go:
idly ext
extens
y spr ensive
spread ive diseas
eading
ing diseas
disease.
dis easee
e.
responding best.2
However, patients with smaller areas of involvement
In contrast to the segmental variant, most cases of 
and less activity may also require phototherapy in
 vitiligo follow an unpredictable course, with periods
some
som e instan
instances
ces bec
becaus
ausee of its superi
superior
or effi
efficac
cacy.
y.
of disease
disease progression
progressionandand quiescence
quiescence.. Early involve-
involve-
3  With all medical interventions, the physical and
ment of the hair follicle is uncommon. Spontaneous
psyc
psychoholog
logic
ical
al impa
impact ct of the
the dise
diseas
asee sh
shoul
ouldd be
repigmentation has been described, although this is
 weighed against the risks of a particular treatment,
not the rule. At present, no medical treatment for
 which typically requires physicians to customize
repigmenting vitiligo has been approved by the US the
th e mana
manage geme
mentnt stra
strate
tegy
gy for each
each pati
patien
ent.
t. In
Food and Drug Administration (FDA), and therefore
ge
gene
neral
ral,, pati
patien
ents
ts sh
shou
ould
ld not
not appl
applyy any
any topi
topica
call
treatments
treat ments are used off-la
off-label.
bel. T
Topical
opical treat
treatments
ments may 
medications
medic ations or sunscr
sunscreen
een before ultraviolet
ultraviolet (UV)
be applied alone when small areas are involved or
light therapy in order to avoid reduced transmission
 when other treatment modalities are not readily 
of UV light into the skin. Patients should also be
availa
ava ilable
ble.. Phototh
Photothera
erapy
py combine
combined d with
with topica
topicall
 vigilant about sun protection to avoid additive effects
treatment is preferred when [5-10% of the BSA is of sun exposure when receiving UV light therapy 
affected or when focal areas are unresponsive to
treatment.
topical treatments alone.
Psoralen plus ultraviole
Psoralen ultraviolett A ligh
lightt photo
phototherap
therapy 
y 
 Topical corticosteroids (level II evidence) (level I evidence)
 When selec
selecting
ting a topical
topical steroid,
steroid, the site of the Psoral
Pso ralen
en plu
pluss ultrav
ultraviole
iolett A lig
light
ht photot
photother
herapy 
apy 
lesion and age of the patient should be considered. (PUVA) was the first phototherapy regimen used in
Lesi
Lesion
onss on th
the
e bo
body
dy may
may be treatreate
ted
d with
with ul
ultra
trapo
pote
tent
nt or patients with vitiligo. The results were reasonable,
potent corticosteroids; the face, neck, and intertrigi- but issues
issues with
with complia
compliance
nce (eg,
(eg, ocul
oculocu
ocutane
taneous
ous
nous areas and lesions in children should be treated pr
prot
otec
ecti
tion
on),
), side
side effe
effect
ctss (eg,
(eg, naus
nausea
ea),
), and
and an
 with either
either midpotency
midpotency topicaltopical corticostero
corticosteroids
ids or increased risk of skin cancer led to a decline in its
calcineurin inhibitors (see below). Possible regimens use. In a recent Cochrane review, PUVAPUVA was deemed
include daily or twice daily application in a cyclical inferio
inferiorr to narrowb
narrowband
and ultrav
ultraviole
iolett B light
light the
therap
rapy 
y 
fash
fashio
ion
n with
with ‘‘da
‘‘days
ys of
off’
f’’’ (eg,
(eg, 1 week
week on ththen
en 1 week
week of
off 
f  (NB-UVB) in achieving [75% repigment
repigmentation in the
6
for 6 months,
followed by 2 or applic
applica
days off).a4tion for 5 consecutive
In practice, days
these regimens general
PU
PUVVA has population
has been laofrgel
been larg vitiligo
ely
y repl patients.
replaced by Therefore,
aced NB-U
NB-UVB
VB,,
appearto
app earto minimi
minimize
ze therisk of advers
adversee effect
effects,
s, alt
althoug
hough
h althoug
although h PUVA may still induce faster repigmenta-
9,10
evidence-based studies to support this are lacking. tion. PUVA may be considered in patients with
 

J A M A CAD
CAD  D ERMATOL  Rodrigues et al    19
 V OLUME
OLUME  77, NUMBER   1
1

Fig 2.   Vitiligo. Lesion on the lower leg before excimer

Fig 1.  Vitiligo. Carnation pink color of vitiligo in a patient laser treatment.
bein
being
g trea
treate
ted
d with
with nanarr
rrow
owba
band
nd ultr
ultrav
avioiole
lett B ligh
lightt
phototherapy.

darker Fitzpa
darker Fitzpatri
trick
ck ski
skinn phototyp
hototypes
es or those
those with
with
11-13
treatment-resistant vitiligo.

NB-UVB (level I evidence)

In addi
additio
tion
n to its immunos
immunosupp uppres
ressiv
sivee eff
effect
ects,
s,
NB-U
NB -UVB
VB indu
induces
ces melanocyte
lanocyte differentia
differentiation
tion and
14
melanin production. In the last decade, NB-UVB
has become
become the firs first-l
t-line
ine therap
therapyy for extens
extensive
ive,,
progre
pro gressi
ssive
ve vitili
vitiligo
go bec
becausause e of its sup
superi
eriorit
ority
y to
PUVA and its relative paucity of side effects. It can
also
also be used
used sa safe
fely
ly in child
childre
ren
n and
and thos
thosee who
who
ar
are
e prpreg
egna
nantnt or la lact
ctatatin
ing.
g. Wh
Whenen used
used alonalone,
e,
repigm
rep igment
entati
ation
on rat
rates
es ranging
ranging from 40% to 100% 100%
have been repo
been  reported,
rted, depending on the location of 
the lesions.15-19 Patients should be treated with an Fig 3.  Vitiligo. Lesion on the lower leg (with pigmented
optimized, aggressive approach, starting at a safe, hairs, which portend a favorable prognosis) after 7 months
low dose (ie, 200 mJ) 2 to 3 times per week with 10% of excimer laser therapy.
to 20% dose increments. When asymptomatic, light typically fails to stabilize vitiligo because clinically 
pink erythema (Fig(Fig 1)1) lasting \24 hours is achieved, unaffec
una ffected
ted skin
skin is not treate
treated.
d. In the segme
segmentantall
the optimal dose has been reached and treatment  variant, excimer laser seems to be the most benef icial
icial
sh
shou
ould
ld cont
contininue
ue at th this
is dose
dose unti
untill er
eryt
ythe
hemama treatment when used early in the disease course.21 In
disappears. The d
The dose
ose should then be increased again a recent retrospective study, 59 patients with the
20
until it returns. The maximum dose of NB-UVB segmental variant, which is typically refractory to
 varies depending on Fitzpatrick skin phototype and treatment, responded well to excimer laser, topical
photosensitivity. There are no established guidelines tacrolimus, and short-term systemic corticosteroids
for maximum dosing for vitiligo, and we therefore for 3 months; alm
almost 50% of patients achieved [75%
recomm
recommend end inc
increas
reasing
ing the dosdosee until
until lig
light
ht pink
pink repigmentation.22
erythema is achieved or until side effects (such as
skin
skin burning,
burning, sesensit
nsitivi
ivity,
ty, pee
peelin
ling,
g, or thithicke
ckenin
ning)
g)
Oral immunosuppression (level III-2 evidence)
develop. A lack of response after 6 months suggests
Or
Oral
al ste
steroid
roidss may help help stab
stabil
iliz
ize
e raprapidly 
idly 
a non
nonres
respon
ponsiv
sive
e pat
patien
ient,
t, and   discont
iscontinuat
inuation
ion of 
11 progressive disease. Oral minipulse therapy (OMP)
treatment should be considered.
refe
refers
rs to thethe disc
discon
onti
tinu
nuou
ouss admi
admini
nist
stra
rati
tion
on of 
suprapharmacologic doses of steroids. Randomized
 Targeted UVB phototherapy (level II) controlled trials investigating their efficacy are still
Targ
Target
eted
ed phot
phototothe
hera
rapy
py (exc
(excim
imer
er lase
lasers
rs and
and lacking,
lackin g, although
although numero
numerousus retros
retrospectiv
pectivee studies
studies
excimer lamps)
lamps)  can be considered when \10% of  su
supp
pport
ort thei
theirr use
use in progr
progres
essi
sive
ve disea
diseasese.. The
The
2
BSA iswish
 who affected. This therapy
to avoid is attractive for
skin darkening patients
caused by  regime
regimenn consist
consistssforof3 to
dexamethasone low-do
low
6 -dose
se bet
monthsbetame
onametha
thason
sone
e or
2 consecutive
NB-UVB (Figs
(Figs 2   and   3). Although effective in the days. It is usually administered in combina
combi nation
tion with
23
repigmentation of stable lesions, this focal therapy  other therapies, including phototherapy. In initial
 

20   Rodrigues
Rodrigues et
et al  J A M A CAD
CAD  D ERMATOL
JULY  2017
  2017

reports, 5 mg betamethasone/dexametha
betamethasone/dexamethasone sone was significant. Facial lesions responded best, with most
24,25
used on 2 consecutive days per week. This was patients tolerating treatment well. While small, this
incr
increa
ease
sed
d to 7.5 mg/ g/da
dayy in nonrnonresespo
pond
ndererss study provides evidence of efficacy for the treatment
and
and decre
decreas
ased
ed back
back to 5 mg/dmg/dayay when
when dis
disea
easese of vitilig
vitiligo
o with
withtacr
tacrolim
olimus
us (le
(level
vel of evi
eviden
dencece I, stre
strength
ngth
progression was arrested. The results showed that of recommendation
recommendation A).
89% of patients were stabilized within 1 to 3 months.  Another study evaluated 100 children with vitiligo
In anot
anothe
herr st
study
udy,, dexa
dexamemeth
thas
asone
one 10 mg tw twicice
e treated   wi
with
th tacro
tacrolim
limus
us,, clobe
clobeta taso
sol,
l, or placplaceb
eboo
39
 weekly for   #24 weeks halted diseadisease
se progression ointment. The clobetasol-treated group received
in 88% of patients after 18.2 weeks. However, 69%
26 intermittent therapy and others continuous therapy;
experi
exp erienc
enced
ed sid
side
e eff
effect
ects,
s, incl
includi
uding
ng weight
weight gain,
gain, the clobeta
clobetasol
sol-tr
-treat
eated
ed gro
groupup receiv
received ed clo
clobet
betaso
asoll
insomnia,
insom nia, acne, agitation,
agitation, menstrual
menstrual irregulariti
irregularities,
es, ointment for 2 months, petroleum jelly for the next
and hypertrichosis. 2 months, and clobetasol again for the remaining
2 months.
months. The tacroltacrolimus-
imus-treat
treateded group received
Other immunosuppressants and biologics 0.1% ointment for 6 months, and the placebo-treated
Limi
Limite
ted
d da
data
ta are
are avai
availa
labl
ble
e foforr the
the us
use e of othe
otherr group
grou p receiv
received
ed petpetrole
roleum
um jel jelly
ly cont
continu
inuousl
ously y for
immun
immunosuosuppr
ppres
essan
santt drugs
drugs in vi vitil
tiligo
igo.. In a recent
recent 6 month
months. s. Ther
There e wa
wass no stat statis
isti
tica
call
lly
y sign
signifi
ifica
cant
nt
ra
rand
ndomomiz
ized
ed comp
compar arat
ativ
ive
e stud
study,
y, lo low-
w-dodose
se oral
oral difference
differ ence betwe
between en the tacrolimus
tacrolimus and clobetasol
clobetasol
methotrexate was reported to be comparable to OMP, groups,
grou ps, althoug
although h facial
facial lesions
lesions respon
respondedded bet better
ter
and su
sugge
ggest
sted
ed when
when OMP is contra
contraind indica
icate
ted,
d, alt
altho
hough
ugh than
tha n nonfaci
nonfacial
al lesions
lesions oveoveral
rall.
l. Bot
Both h treatm
treatmententss
27
responses were marginal with small study sizes.  were superior to placebo (level of evidence I,
 Antie
 Antietumor necros
necrosisis facto
factor-
r-a   drugs   ha ha ve
 ve been strength of recommendation A).
28,29
suggested for the treatment of vitiligo despite  A small study of 10 patients with bilaterally 
repo
reportrtss of with
 worsening no bene
betheir
nefi
fitt administration.
an
andd eveven
en ininitiati
itiation
30-34on an
and
Twiced symm
sy
cl mmet
clobe
obeta etri
rica
tasol
solcallcr ge
gene
crea
eammneral
raliz
on ized
ed side
one viti
vitili
ligo
go thtrea
treeate
of the ted
body
bo ddy with
wi
anth
andd
dail
dailyy oral
oral cycyclo
cloph
phos
osph
phamamididee (50
(50 mg)
mg) has has al
also
so pim
pimecr crol
olim
imusus cr cre
eam on the the otheotherr shshowowe ed a
demo
demonstnstrat
rated
ed rerepig
pigme
ment ntat
ation
ion in 29 pati patien
ents
ts,, compar
com parabl
able
e degdegree
ree of repigm
repigment entati
ation,
on, althoug
although h
includ
inc luding
ing tho
those
se with
with dif
difficu
ficult
lt to tre
treat
at acral
acral site
sites, small numbers make make   noninferiority
noninferiority trials like this
40
alt
althoug
hough h signifi
significan
cantt side
side effeffect
ectss wer
were e report ed.35
reported. difficult
diffi cult to interpr
interpret.et. (level
(level of evi
eviden
dence
ce II-I,
II-I, streng
strengthth
 Although spontaneous remissions are uncommon of recommendation B).
in patients with vitiligo, treatment recommendations  NB-UVB versus PUVA. PUVA.   NB-U
NB-UVB VB ther
therap
apy y has
has
based on uncontrolled studies should be weighed become the predominant form of phototherapy for
against that possibility.  vitiligo because of its efficacy, relative lack of side
ef
effe
fects
cts,, and
and convconvenenieience
nce.. A stud studyy comp
compari aring
ng
Other treatments
treatments 12 months of twice weekly NB-UVB to twice weekly 
 Vitamin D analogs (level III-I evidence).   Most orall 8-me
ora 8-meth thoxy
oxyps
psor
oralalen
en PUV PUVA demo demons nstr
trat
ated
ed
studies have evaluated calcipotriene in combination superior repigmentation, color matching, a matching,  and nd fewer
11
 with other therapies, particularly phototherapy. side effects in the NB-UVBe
NB-UVBetreated group. Overall,
Ca
Calci
lcipo
potri
trien
ene e may
may sh short
orten
en th the
e ti
time
me to achi achievevee 64% of the NB-UVB group had [50% improvement
re
repi
pigm
gmenenta
tati
tion
on andand re redu
duce
ce overa
overallll cumu
cumula lati
tive
ve in BSA affected versus 36% in the PUVA group. The
ex
expo
posu
sure
re durin
during g phot
phototh
other
erap
apy,
y, but
but it has has not superiority of NB-UVB was maintained 12 months
demonstrated
demonstrat ed   apprecia
appreciable ble repigm
repigmententati
ation
on when
when after
after treatm
treatmentent end
ended
ed (level
(level of evi
evidendence
ce I, streng
strength th of 
used alone.36,37 recommendation A).
Othe
Otherr tr trea
eatmtmen
ents
ts for vi viti
tili
ligo
go appe
appearareded to be  Another investigator-blinded trial of NB-UVB
promising in pilot trials but failed to demonstrate  versus PUVA PUVA 3 times per week for 6 months was
signifi
significant
cant effi
efficac
cacyy in later
later cont
controll
rolled
ed trials
trials.. Exa
Exampl
mpleses conducted in 56 patients.41 Median repigmentation
include   Polypodium leucotomas , gi
Polypodium leucotomas  gink
nkggo bi bilo
loba
ba,,  was similar between the 2 groups but adverse effects,
38
antioxidants, and pseudocatalase cream. part
particu
iculalarly
rly prurit
pruritus
us,, wewere
re mumuch ch lowe
lowerr in the the
Compara
Com parative
tive effic
efficacyacy studies.
studies.   Topical steroids  NB-UVB
NB- UVB group
group (7.4%
(7.4% vs 57. 57.2%)
2%).. The face, neck, neck,
versus calcineurin inhibitors.   There have
calcineurin inhibitors. have been a few few and
and truntrunk k demo
demons nstr
trat
ated
ed the
the bestbest resp
respononsese in
studie
studiess comparin
comparing g different
different treatme
treatmentsnts for vitili
vitiligo.
go. In 1 both
both grougroups ps (lev
(level
el of ev evid
iden
encece I, stre
strengngth
th of 
study
study,, ta
tacro
crolimlimus
us ointm
ointmenentt 0.0.1%
1% was co commpared recommendation A).
7
 with clobetasol
clobetasol cream 0.05% in children. This Combination
Combinatio
been promotendtherapies.
promoted therapies
for vari .   Although
various
ous Althoughanti
skin antioxida
diseasoxidants
diseases, ntshave
have
es, including
including
randomized, double-blind, comparative trial revealed
49% repigmentation with clobetasol and 41% with  vitiligo
 vitiligo,, few controlle
controlledd studstudies
ies have atteattempt
mpted
ed
tacrolim
tacrolimus,
us, but the differen
difference
ce was not stat
statist
istical
ically 
ly  to dete
determi
rmine
ne their
their tru
true
e effica
efficacy.
cy. In 1 random
randomizeized,
d,
 

J A M A CAD
CAD  D ERMATOL  Rodrigues et al    21
 V OLUME
OLUME  77, NUMBER   1
1

Fig 4.  Vitiligo. Lesion on the upper aspect of the back

before narrowband ultraviolet B light phototherapy.
Fig 5.  Vitiligo. Lesion on the upper aspect of the back
afte
afterr 5 mo
mont nths
hs of na
narr
rrow
owba
band
nd ul
ultr
trav
avio
iole
lett B li
ligh
ghtt
phototherapy.
double-blind,
double-blind, placebo-
placebo-cont
controlle
rolled study,42 patients
d study,
received a combination of   a-lip
-lipoic
oic acid,
acid, vitamin
vitamin C,
 vit
 vitamin
amin E, and polyunsatur
polyunsaturated
ated fatty acids or placebo
placebo  Maintenance therapy.   G
Giv
iven
en that
that the
the risk
risk of 
for 2 months. They were then treated with NB-UVB
NB-UVB for relapse   in the
relapse the firs
firstt year
year afte
afterr ceas
ceasin
ing
g ther
therap
apyy is
45
6 months. Forty-seven percent of those treated with 44%, it may be import important
ant to tra
transi
nsitio
tion
n pat
patien
ients
ts
antioxid
antioxidants
ants before
before NB-UVB
NB-UVB dem demonst
onstrate
ratedd   [75% to mainte
maintenanc
nancee therap
therapy y once repigm
repigment
entati
ation
on is
re
repi
pigm
gmen
enta
tati
tion
on vers
versus
us 18
18%
% in th thee pl
plac
aceb
eboo pl
plus
us achieved. In 1 study, all patients achieving [75%

NB-UVB
contro
con trolledgroup.
lled tri
trial Although
al suppor
sup ports
ts the thisuse
is aofsingle
antioxstudy,
antioxida ntsthis
idants in repigmentation
either tacrolimusfrom any modality
ointment were treated
0.1% or placebo with
ointment
patients undergoing phototherapy (level of evidence twice weekly. Thirt
Thirt y-five
 y-five patients were enrolled in
46
I, strength of recommendation A). this 24-week trial. Lesions on the hands and feet
 Evidence for treatment regimens.   There is little  were excluded. Ninety-six percent of those treated
evidence to guide clinicians on selecting the optimal  with tacrolimus on the head and neck maintained the
fre
freque
quency
ncy,, dosing
dosing,, and duratio
duration n of tretreatm
atment
ent for repigmente
repigm entedd areas without relapse, while only 60%
 vitiligo. No comparative studies have been on plac
placeb
eboo were
were main mainta
tain
ined
ed.. Succ
Succesesss of the the
performed on one topical dosing frequency versus mainte
mai ntenan
nance
ce therapy
therapy was indepeindepende
ndent nt of initial
initial
anot
anotheherr, 2 titime
mess week
weekly ly vevers
rsus
us 3 ti time
mess we week
ekly 
ly  tre
treatm
atment
ent mod
modaliality.
ty. Topic
Topical
al tacroli
tacrolimus
mus ointmen
ointmentt
phot
hotot
othe
hera
rapy
py,, or on di diffffer
eren
entt dos
doses of or oral
al 0.1% twice weekly can therefore be recommended
corticosteroids for active vitiligo. Two have studied for maintenance therapy (level of evidence II; Figs II; Figs 6
differences in efficacy between 2 and 3 times weekly  we ekly  and 7). Som
Some e hav
havee sug
sugges
gested
ted a sim
simila
ilarr appr
approac
oach h with
tre
treatm
atment
entss with
with the excime
excimerr laser
laser for vitili go.43,44
vitiligo. NB-UVB
NB- UVB to preven
preventt relaps
relapse,
e, but no stu studie
diess hav
havee
Bo
Bothth concl
conclududed
ed ththat
at th
there
ere wa wass no di diffe
ffere
renc
nce
e in tested the efficacy of this approach.
the final degree of repigmentation between the 2
dosing frequencies;
frequencies; however,
however, repigmentat
repigmentation ion was
SURGICAL TECHNIQUES
depe
depend nden
entt on th thee totota
tall numb
number er of treatreatm
tmenentt Key points
sessions, with earlier onset of pigmentation noted d Surgical
Surgic al tec
techni
hniqu
ques
es are most
most suc
succes
cessfu
sfull in 
 with 3 times weekly dosing. This is likely to be the late-stage segmental vitiligo
case for NB-UVB also. d Su
Surge
rgery
ry can
can be cons
consid
idere
ered
d in th
those
ose with 
with 
Regarding duration of therapy, a previous study  nonresponsive, stable vitiligo
reported a mean 25% improvement after 3 months, d Nonc
No nculultu
tured
red epepid
iderm
ermalal mela
melano
nocy
cyte
te cell 
cell 
50% after 6 mont months,
hs, and 75% after 9 months of  graftin
gra fting
g dem
demons
onstrat
trates
es sup
superi
erior
or exte
extent
nt and
11
NB-UVB
NB-U therapy  (Figs 4   and   5). The slow but
VB therapy  quali
quality
ty of pigm
pigmen
entat
tatio
ion
n comp
compare
ared
d with 
with 
steady improvement when undergoing therapy for other surgical techniques
 vitiligo requires patience and motivation on the part
of the patien
patientt and cli
clinici
nician.
an. Monito
Monitorin
ringg improv
improveme ementnt Surgical treatments offer some of the best results
requires baseline and serial images at each visit. As for stable vitiligo. Repigmentation can improve by 
$
long
tol as
tolera the
erable
ble, patient
, tre
treatm entiscan
atment improving andd side
be continue
continued untileffects
until arer
no furthe
further 68
68%
tre % ent
treatm
atment in cert
ce rtai
ain
sessio
ses nn.
  ty 
sion. 47p
pes
e When
s of vitvitrepigmentation
ilig
iligo
o wi
with
th only
only  is1
impr
improv
ovem
emen entt occur
occurs,s, afte
afterr which
which main
maintetena
nance
nce obtaine
obt ained d in the
these
se pat
patien
ients
ts,, relaps
relapse
e is unco
uncommo
mmon. n.48,49
treatment can be initiated. Severa
Sev erall sur
surgica
gicall opt
options
ions exis
exist,t, whi
which
ch can be cla
classi
ssifie
fied
d
 

22   Rodrigues
Rodrigues et
et al  J A M A CAD
CAD  D ERMATOL
JULY  2017
  2017

Fig 6.   V
Vit
itil
ilig
igo.
o. De
Depig
pigme
ment
nted
ed patc
patch
h on bu
butto
ttock
ck an
andd
scro
scrotu
tum
m of ba baby
by boy
boy that
that re
repi
pigm
gmen
ente
ted
d with
with top
topic
ical
al
therapy.
Fi
Fig
g 8.   Vit
Vitilig
iligo.
o. Lesion
Lesion on left uppe
upperr eye
eyelid
lid befo
before
re trea
treatmen
tment.
t.

Fig 7.  Vitiligo. After 13 months of maintenance therapy 

 with twice weekly tacrolimus, pigmentation has been Fig 9.   Vitiligo.
Vitiligo. Lesion on left upper eyelid 9 months after
maintained
mainta ined on the buttock and scrotu
scrotum.
m. punch grafting. The hyper
hyperpigmen
pigmentation
tation and cobbl
cobblestone
estone
appearance of the punch grafts usually subside with time.

into tissue and cellular grafts. Tissue grafts usually  Koebnerizat

Koebne rization,
ion, confetti-li
confetti-likeke lesions,
lesions, inflam
inflammator
matory  y 
transfer solid tissue from donor to recipient site in a  vitiligo, and trichrome vitiligo are also indicators of 
1:1 rat
ratio.
io. Cellula
Cellularr grafts
grafts cover
cover lar
larger
ger surfac
surface
e are
areas
as and unstable disease and are discussed in detail in the
are composed of suspensions of keratinocytes and fi
firs
rstt article
rticle in thisthis con
continu
tinuing
ing memedic
dical
al edu
educati
cation
on
52,53
melanocytes in a donor to recipient ratio up to 1:10. series.
Recip
Recipie ient
nt site
site is anoth
another er varia
variabl
blee that
that sho
should
uld
Patient selection  be consconsidider
ered
ed.. In ge genenera
ral,
l, the
the head   an and d neck
neck
Patient selection is key to success with surgical de
demomonstnstra
rate
te a supesuperioriorr res
respon
ponsese..55,56  Acrofaciall
 Acrofacia
treatment for vitiligo. Those with stable disease have dis
disea
easese and are
areas
as ove
overr joint
jointss res
respon
pond d poo
poorly
rly,, pos
possi
sibly 
bly 
a superior response to surgical intervention. Patients because of repeate
repeated d motion or friction and injury at
55,56
 with segmental disease have better results than those these locations. Patients must be screened for a
 with focal disease who, in turn, fare better than hi
hist
stor
ory
y of kelo keloid ids,
s, coag
coagul ulat
atio
ion
n abnoabnorm rmalalit
itie
ies,
s,
patients with generalized, unstable vitiligo. 50-53 bloodborne infections, and other contraindication
contraindicationss
Disease stability must be evaluated before surgery  to surgery, such as severe heart disease.
and is defined by the absence of new or expanding
lesions over 6 months to 2 years. Several methods
can be used to assess stability, such as patient report,  Tissue grafts
serial photography, and validated scoring systems. Minipunch grafts are performed by placing 1- to
These include changes in the Vitiligo Area Scoring 1.5-mm punch biopsy specimens from a donor site
Index, Vitiligo European Task Force assessment, and into a preprepared recipient site (Figs
(Figs 8 and
8  and 9
 9).
). This
 Vitiligo Disease Activity Score. In cases where technically
techni cally simple, inexpensiv
inexpensive
e techni
technique
que does not
stab
stabil
ilit
ity
y or a test
performing tr
trea
eatm
tmen
entt outc
outcom
procedure omee a is
with unce
uncert
single rtai
ain,
punch n, req
require
uire spe
perform specia
oncialize
lized
large dareas,
equi
equipme
pment
can nt butto ispigment
lead difficul
difficulttand
to
graft in the center of a stable, depigmented lesion
lesion to textural variations such as cobbles
cob blestoning,
toning, and carries
assess the degree of repigmentation is useful. 53,54 a risk of scarring and keloids. 57-60
 

J A M A CAD
CAD  D ERMATOL  Rodrigues et al    23
 V OLUME
OLUME  77, NUMBER   1
1

Fig 10.   Vitiligo. Harvesting of suction blister grafts.   Fig 11.   Vitiligo. Segmental variant of vitiligo on the left
upper forehead at baseline.
Suction
Suction bli
bliste
sterr epiderm
epidermalal grafti
grafting
ng involve
involvess the
creation and transfer of blister roofs from normal
skin (Fig 10) to ab abra
rade
dedd depi
depigmgmenente
ted
d skin
skin..
 Advantages include low cost, use of simple
eq
equi
uipm
pmen
ent,
t, unifo
uniform rm colo
colorr matc
match,
h, lolow
w rate
ratess of 
scarring, and good efficacy. The time required to
create blisters   and risk  of hemorrhagic blisters are
disadvantages.57-59,61-63

Cellular grafts
Cellular grafts can be cultured or noncultured and
involve
invol ve creating a cellular
cellular suspension
suspension from a thin to
ultrathin skin graft. Noncultured options, although
complex, do not require a full cell culture laboratory. Fig 12.   Vitiligo. Segmental variant of vitiligo on the left
upper forehead
forehead 9 monthmonthss after noncultur
noncultureded epider
epidermal
mal
Ther
Theref efore
ore,, non noncul
cultu
ture
redd ep epid
iderm
ermalal su susp
spen
ensi
sion
on
suspension grafting.
(NCE
(NCES) S) grgraf
afti
ting
ng,, alalso
so know
known n as a mela melano nocy
cyte
te
kerati
ker atinoc
nocyte
yte tratransp
nsplan
lantt proc
procedu
edure,
re, is perform
performed ed Comparative efficacy 
more frequently than culture culturedd melanocyte
melanocyte grafting. NCES has shown superior extent and quality   of 
It is now co consider
nsidered ed the criter
criterion
ion stan
standard
dard for vitiligo
vitiligo repigm
repigment
entati
ation
on compar
compareded wit
with
h bliste
blisterr gra
grafti ng.67
fting.
grafting worldwide. Howeve
How everr, bliste
blisterr gra
grafti
fting
ng and punch
punch graftin
graftingg are
NCES is performed by harvesting an ultrathin skin much easier techniques to master and require fewer
graft from a donor site, which is then incubated in support staff.
try
trypsi
psin.
n. Aft
Afterer remova
removall of the epidermepidermis is from the
dermis
der mis,, the epiderm
epidermis is is manual
manually ly dis
disrupt
rupteded and then
then
centrif
cen trifuge
uged d to obtain
obtain the cellula
cellularr pellet
pellet,, whi
which
ch is Camouflage techniques
Camouflage may be an important part of overall
re
resu
susp
spen
endeded d in Ri Ring
ngers
ers lact
lactat
ate,
e, appl
applieiedd to th thee
patient management given the aesthetic impact of 
abrade
abr aded d rec
recipi
ipient
ent sitsite,
e, and dresse
dressed.d. Moveme
Movement nt
the diseas
disease
e in man
many y patien
patients
ts.. Sel
Self-t
f-tanni
anning
ng age
agents
nts
sh
shouould
ld be re rest
stri
ricte
cted d post
postop
opererat
ativ
ivel
ely
y to avoi avoid d
provide waterproof protection for 3 to 5 days; highly 
dressing displacement, but bed rest is not required.
pigmented cover creams require daily application
Dressings are removed between days 4 and 7. This
but are lightweight and waterproof. While dermal
procedure yields good cosmetic results and color
pigmentation can be achieved with techniques like
match (Figs
(Figs 1111   and 
and   12
12).). Disadvantages include the
cosm
cosmetetic
ic tatt
tattoo
ooin
ing,
g, pote
potent
ntia
iall risk
riskss sh
shou
ould
ld be
cost, need for specialized equipment and a skilled
care
careful
fully
ly cons
consid
idere
ered.
d. Thes
Thesee risrisks
ks inclu
include
de thethe
team, andand limitations
limitations of sites that can be successfully 
47,51 potential for infection, risk of koebnerizing vitiligo,
treated.  A new method using epidermal su suct
ction
ion
64 lack of legislation on tattoo pigments, poor color
blisters for donor skin has also been described. Of 
match, bleeding of color over time, and potentia
potentiall for
note, battery-operated cell harvesting devices have
spread of the lesion beyond the tattoo border.68
also
also been
been deve develop
loped ed,, offer
offerin
ingg a self
self-c
-con
ontai
taine
ned d
syst
system
em
additi
add for
itiona
onal ce
cell
llipment
l equipm
equ se
sepa
para
rati
. tion
ent. on dwith
Head
Hea wito
thou
out
head
hea t dth
the
e need
neparison
ed son
compari
com fo
forr  TREATMENT
 TREATMENT ALGORITHM
studi
tudiees to sta tand
ndar
ard
d NCE CESS ti tisssu
suee   processing
processing Treatment for vitiligo should be started as early as
techniques have not yet been performed.65,66 possible to maximize efficacy. The type of vitiligo,
 

24   Rodrigues
Rodrigues et
et al  J A M A CAD
CAD  D ERMATOL
JULY  2017
  2017

 Topical therapies
Repo
Report rted
ed sideside effe
effect
ctss of inapinapprpropopri
riat
atee or
unsupe
uns upervis
rvised
ed topica
topicall steroid
steroidss inc
includ
lude e cut
cutane
aneous
ous
atrophy,
atroph y, telan
telangiecta
giectasias,
sias, hype
hypertrichos
rtrichosis,
is, acne, and
striae
striae.. However
However,, its side side effect
effect profile
profile has been been
deem
deemed ed favo
favorab
rable
le wh
whenen used
used as pr pres
escri
cribe
bedd by 
dermatologists for atopic dermatitis, in which there
is epi
epiderm
dermal al barr
barrier
ier dysfun
dysfunctio
ctionn   and a grea greate
terr
likelihood
likel ihood of systemic
systemic absorption.
absorption. To minim
69 minimizeize
the risk of side effects, a sequential discontinuous
scheme may be used.
Topical tacrolimus lacks the side effect profile of 
topi
to pica
call ster
steroid
oidss and
and appe
appearsars to be mu muchch safe
saferr,
particularly on sensitive areas like the face, genitals,
and intertriginous sites. When topical tacrolimus first
became
bec ame availa
available
ble for use,
use, con
concern
cernss were
were raised
raised
abou
aboutt thethe risk
risk of mali
maligngnan
anci
cies
es that
that hadhad been
been
observed in those taking large oral doses to prevent
tran
transp
spla
lant
nt orga
organ n reje
reject
ctio
ion.
n. Howev
However er,, a rece
recent
nt
system
sys temati
aticc review
review and metaan
metaanaly alysis
sis rep
report
orting
ing on
Fig 13.  Treatment algorithm for the segmental variant of  the risk of lymphoma in those with atopic dermatitis
 vitiligo.. NB-UVB , Narrowband ultraviolet light phototherapy;
 vitiligo concluded that it does not appear to significantly 
TCS , topic
topical
al cort
corticos
icosteroids; TIM , topic
teroids; topical
al immun
immunomod
omodulato
ulators.
rs. contribute to the overa
overall ll risk of lymphoma in this
subgroup of patients.70 Nevertheless, this black box
extent and duration of disease, effect on quality of   warning remains and it is still not approved by the
life,
life, and previo
previous us tre
treatm
atmententss should
should determi
determine ne FDA, Therapeutic Goods Administration (Australia),
the
the in init
itia
iall trtrea
eatmtmen
entt appr
approac
oach. h. TheThe segm
segmen ental
tal or the European Medicines Agency for use in vitiligo.
 variant, when treated early in the disease course If burn
burning
ing after
after app
applic
licati
ation
on of tac
tacroli
rolimus
mus is not
noted,
ed, the
(#12 month onthss), ca can
n be in inititia
iall
lly
y treat
reated
ed witwith concentration
concen tration m
mayay be decrea
decreased.sed. Wh
While
ile skin flu
flushing
shing
skin-directe
skin- directed d medical
medical therapy.
therapy. In nonres nonresponsiv
ponsive e or may occur immediately after alcohol ingestion and is
longst
lon gstand
anding
ing sta stable
ble disdiseas
ease, e, surgic
surgicalal therapi
therapies
es not always
always lim
limiited
ted to thethe area
area of appl
applic
icat
atio
ion,
n, it
should be considered (Fig (Fig 13
13). ). resolves quickly. 71

The exte
extent
nt of involv
involvememenentt alsalso o de
deter
termi
mines
nes the
tre
treat
atme
mentnt approa
approach ch in vi vitil
tiligo
igo.. Locali
Localized
zed disdisea
ease
se Phototherapy 
(#5-10% of BSA) is best treated with topical therapy   While an absence of melanin in lesional skin and
and tar
targete
geted d photother
phototherapy,apy,whil
while e a combinat
combinationion of NB- prolonged administration of phototherapy may give
UVB
UV B andtop
and topicaicall therap
therapy y is use
used d to tre
treat
at more
more exte
extensi
nsive
ve ri
rise
se to conc
concern
ern abou
aboutt the
the deve
develolopm
pmenentt of sk
skin
in canc
cancer
er
disease ([5-10% of BSA). OMP can be added for those in this population, recent evidence suggests that the
 with clinical
clinical signs
signs of aggress
aggressive,
ive, progress
progressive
ive dise
disease
ase genetic and autoimmune profile of vitiligo patients
(Fig 14
14).
). Effi
Efficacy
cacy can be assess
assessed
ed at approxim
approximatel
ately 
y  confers
conf ers a deg
degree
ree of pro
protec
tectio
tion
n aga
agains
instt me
melano
lanoma
ma and
and
6 months based on twice-weekly NB-UVB. nonmela
nonm elanom
nomaa skinskin cancer
cancerss (NMSCs
(NMSCs). ).72-78  While
prolonged PUVA for psoriasis increases the risk of 
 TREATMENT SAFETY 
 TREATMENT cutaneous malignancies in white patie
white  patients,
nts, the same
79,80
Key points has not been noted with NB-UVB. Even studies
d  Topical corticosteroids, when used as of PUVA for vitiligo do not appearappear to be
to  be associated
81,82
directed and with dermatologic supervision,  with the development o
development off NMSCs.
appear to be safe and are usually efficacious  While Hexsel et al83 rep report
orted
ed a hig
higher
her annual
annual
for vitili
vitiligo
go incidence of NMSC in those with vitiligo compared
d Despit
Des pite
e evi
eviden
dence
ce that
that tacrol
tacrolimu
imuss doe
doess not   with the rest of the population, 5 other studies reveal
appear to increase the risk of malignancy, its lo
lowe
werr rat
rate
es of melanom noma and NMSC in this his
84-88
 black box warning remains population. In addition, a 2005 review of the
d

Lon
Long-t
g-term
appear erm admini
administra
to increasestratio
tion
n of NB-UVB
incidence NB-UVB do
does
es not 
of melanoma or  literature
B ligh suggested
lightt doe
does   no that
em chronic
nott seem
se to incr
increause
seofthe
ease thultraviolet
e risk
risk of 
89
nonmel
non melano
anoma
ma ski
skin
n cancers
cancers in tho
those
se with  ski
skin cancer.. Limi
n cancer Limita
tati
tions
ons exis
existt for
for all
all of thes
these
e
 vitiligo studies, highlighting the need for well-constructed
 

J A M A CAD
CAD  D ERMATOL  Rodrigues et al    25
 V OLUME
OLUME  77, NUMBER   1
1

Vitiligo

≤5-10% BSA >5-10% BSA

TCS; TIM + targeted Aggressive/rapidly Nonaggressive/not

NBUVB progressive rapidly progressive

No response (lack of Response (stable at 3

stability at 3 months, months, OMP + NBUVB +
TMI NBUVB+TCS/TIM
no repigmentation at 6 repigmentation at 6 TCS/TMI
months) months

Continue treatment No response at 6

stable 1 year or more and review at 3 month Response at 6 months
months
intervals No response at 6
Response at 3 months
months

Continue treatment
and review at 3 month
Surgical therapy intervals
Cosmetic camoulage
Stop OMP and continue
NBUVB + TCS/TMI with
3 month intervals

Depigment (if
extensive - >70%BSA)
extensive >70%BSA)

Fig 14.  Treatment algorithm for vitiligo.

prospective randomized controlled trials that span of 48.64% and 33.26% at day 168, respectively. Side
decades. effects   inclu
ncluded
ded hype
hyperpi
rpigm
gmen
enta
tati
tion,
on, itch,
itch, and
and
90
nausea.  Additional studies with this promising
Surgical treatments treatment are warranted.
Co
Comp
mpli
lica
cati
tion
onss ar
are
e rare
rare wi
with
th most
most su surg
rgic
ical
al
proced
procedure
uress but include
include pain,
pain, hypop
hypopigmigmentation,
entation,  Targeted immunotherapy 
47,60
koebnerization, scarring, and infection. In the first article in this series, we outlined recent
tra
transl
nslati
ational
onal resresear
earch
ch thathatt has provid provided ed insigh
insightt
in
into
to po posssible
ible targe
argetsts forfor tar targete
geted d thera
herappies
ies
EMERGING
Key points TREATMENT
TREATMENT MODALITIES for viti
vitili
ligo
go.. In part
partic
icul
ular
ar,, inte
interfe
rferin
ringg with
with thethe
d  Afamelanotide enhances the efficacy of  interferon (IFN)-g -CXCL10
-CXCL10 chemokine axis may be
NB-UVB in patients with vitiligo an effect
effective
ive strat
strateg
eg y to develop novel, targeted
d  Targeted immunotherapy has been safe immunotherapies.91 Significant repigmentation of   2
an
andd effec
effectiv
tive
e fo
forr psor
psoria
iasi
sis,
s, an
andd a simil
similar 
ar  patients
patie nts after the oral administra
administration tofacitinib92
tion of tofacitinib
treatmentt strateg
treatmen strategyy may be equal
equally
ly benefi
beneficial 
cial  (a pa pan
ne J  Jan
anus
us kina
kinase
se inhi
inhibitbitor
or [JA[JAK K 1/3)
1/3)])
]) and
and
93
for vitili
vitiligo
go patients
patients ruxolitinib (JAK (JAK 1/21/2 inhib
inhibit itor)
or),, whwhich
ich dir
direc
ectl
tly 
y 
d  The interferon-g -CXCL1
-CXCL100 che
chemok
mokine
ine axi
axiss inhibit
inh ibit IFN-
IFN-g    si
signa
gnalin
ling,
g, sup
suppor portsts this
this con
concep
cept.t.
appe
ap pear
arss to be an im impo
porta
rtant
nt ta
targe
rgett for
for th
thee Howe
Ho weveverr, repi
repigm
gmenenta
tati
tion
on regr regresessesed d whwhenen the
the
development of new treatments for vitiligo patien
pat ientt discon
discontintinued
ued ruxoruxolitilitinib,
nib, sug sugges
gestin
ting
g tha
thatt
continuous treatment is required. Importantly, the
a -Melanocyte-stimulating hormone analogues patient’s serum CXCL10 level was reduced during
 Afamelanotide is a potent synthetic analogue of  trea
treatmtmen
entt with
with ruxo
ruxoliliti
tinib
nib,, su sugg
ggesestiting
ng that
that JA
JAK 
K 
the natural
naturally
ly occ
occurri
urring
ng   a-melanocyte-stimulating in
inhi
hibit
bitio
ionn works
works by targe targeti ting
ng the
the IFN- IFN-g -CXCL10
-CXCL10
horm
hormone
NB
NB-U one.
VB . inIt awas
-UVB wadoubl
s inve
douinvest
e stig
ble igat
bl ated
blin ed mult
ind,
d, as ltic
mu an
icenadju
ad
terrjunct
ente nct to.
study
study. axis, andand
activity thattreatment
it may serve as a biomarker
response. A recent for disease
case series
Patients
Patients treated
treated with NB-UVB
NB-UVB plus afamelanoti
afamelanotide de reported efficacy of topical ruxolitinib
ruxolitin ib   in patients
 versus NB-UVB alone achieved repigmentation rates  with vitiligo, particularly on the face.94  While these
 

26   Rodrigues
Rodrigues et
et al  J A M A CAD
CAD  D ERMATOL
JULY  2017
  2017

advancess are promis

advance promising
ing for vitili
vitiligo
go suffere
sufferers
rs and autoimmun
autoim munee destru
destructi
ction
on of melan
melanocy
ocyte
tess alo
along
ng
dermatologis
dermat ologists
ts alike,
alike, larger,
larger, controlled studies
studies are  with stimulation
stimulatio n of melanocyte regeneration
regenerati on is
required to assess the safety and efficacy of targeted likely to produce the best results. Lack of previous
therapies for vitiligo. success is often the reason for a pessimistic outlook
regarding treatment on the part of both the treating
Depigmentation  physician and the patient; however, education and
For patien
patients ts with
with rec recalc
alcitra
itrant
nt and widewidespr
spread
ead establishing realistic expectations, a comprehensiv
comprehensive e
([50
50%% of BS BSA) A) vi viti
tili
ligo
go,, depi
depigmgment
entat
atio
ion
n of th the e treatment plan, and photography at each visit can
remaining islands of pigment may provide cosmetic result in a successful outcome. Recent advances in
impr
improvovem
emen entt th that
at may
may en enhan
hancece quali
quality
ty of li lif 
f e
e.. determining the pathogenesis of the disease have
Foll
Follow
owiningg it itss di disscove
covery ry in ru rubb
bberer gl glov
ovees95 opened exciting new treatment avenues that may 
more
mo re ththan
an 50 ye year
arss ago,
ago, mono
monobe benz
nzyl
ylet
ethe
herr of  hera
heraldld a revo
revoluluti
tion
on in the
the futu
future
re trea
treatm
tmen
entt of 
hydr
hydroq
oqui
uino
nonene (MBE (MBEH) H) hashas beco
become
me th thee most
most  vitiligo.
commonly used depigmentation therapy for vitiligo
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1

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 Answers to CME examination 

Identification No. JB0717
 July 2017 issue of the Journal of the American Academy of Dermatology.

Rodrigues M, Ezzedine K, Hamzavi I, Pandya AG, Harris JE, Vitiligo Working Group. J Am Acad Dermatol 2017;77:17-29.

1. c 4. e
2. a 5. a
3. a 6. d