Jurnal Melasma 2

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{\info{\author Josefina}{\subject Dermatology}}
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\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-160\slmult0 \fs16
\cf0\f0\charscalex100 {Hindawi Publishing Corporation}\par\pard\li346\ri0\sl-200
\slmult0 \fs16\cf0\f0\charscalex100 {Dermatology Research and Practice}\par\pard
\li346\ri0\sl-186\slmult0 \fs14\cf0\f0\charscalex100 {Volume 2011, Article ID 37
9173, }\fs14\cf0\f0\charscalex100 {5 }\fs14\cf0\f0\charscalex100 {pages}\par\par
d\li346\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {doi:10.1155/2011/379173}\
par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-213\slmult0 \f
s18\cf0\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-213\sl
mult0 \fs18\cf0\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\s
l-386\slmult0 \fs36\cf0\f0\charscalex100\i {Clinical Study}\i0 \par\pard\li346\r
i0\sl-480\slmult0 \fs36\cf0\f0\charscalex100\b {A Double-Blind, Randomized Clini
cal Trial of Niacinamide 4}\b0 \fs36\cf0\f0\charscalex100 {%}\par\pard\li346\ri0
\sl-386\slmult0 \fs36\cf0\f0\charscalex100\b {versus Hydroquinone 4}\b0 \fs36\cf
0\f0\charscalex100 {%}{ }\fs36\cf0\f0\charscalex100\b {in the Treatment of Melas
ma}\b0 \par\pard\li1066\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li1066\ri0\sl-213\
slmult0 \fs18\cf0\par\pard\li1066\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li1066\r
i0\sl-293\slmult0 \fs24\cf0\f0\charscalex100\b {Jose\uc1\u64257Xna Navarrete-Sol
}\b0 \fs24\cf0\f0\charscalex100\b {}\b0 \fs24\cf0\f0\charscalex100\b {\uc1\u305Xs
,}\b0 {\super \fs16\up3\cf0\f0\charscalex100\b {1}\b0 }\fs24\cf0\f0\charscalex10
0\b {Juan Pablo Castanedo-C}\b0 \fs24\cf0\f0\charscalex100\b {}\b0 \fs24\cf0\f0\c
harscalex100\b {azares,}\b0 {\super \fs16\up3\cf0\f0\charscalex100\b {1}\b0 }\fs
22\cf0\f0\charscalex100\b {Bertha Torres- }\b0 \fs22\cf0\f0\charscalex100\b {}\b0
\fs22\cf0\f0\charscalex100\b {Alvarez,}\b0 \fs16\cf0\f0\charscalex100\b {1, 2}\
b0 \par\pard\li1066\ri0\sl-266\slmult0 \fs24\cf0\f0\charscalex100\b {Cuauhtemoc
Oros-Ovalle,}\b0 {\super \fs16\up3\cf0\f0\charscalex100\b {3}\b0 }\fs24\cf0\f0\c
harscalex100\b {Cornelia Fuentes-Ahumada,}\b0 {\super \fs16\up3\cf0\f0\charscale
x100\b {1}\b0 }\fs22\cf0\f0\charscalex100\b {Francisco Javier Gonz}\b0 \fs22\cf0
\f0\charscalex100\b {}\b0 \fs22\cf0\f0\charscalex100\b {alez,}\b0 {\super \fs16\u
p3\cf0\f0\charscalex100\b {4}\b0 }\par\pard\li1066\ri0\sl-266\slmult0 \fs22\cf0\
f0\charscalex100\b {Juan David Mart}\b0 \fs22\cf0\f0\charscalex100\b {}\b0 \fs22\
cf0\f0\charscalex100\b {\uc1\u305Xnez-Ram}\b0 \fs22\cf0\f0\charscalex100\b {}\b0
\fs22\cf0\f0\charscalex100\b {\uc1\u305Xrez,}\b0 {\super \fs16\up3\cf0\f0\charsc
alex100\b {4}\b0 }\fs24\cf0\f0\charscalex100\b {and Benjamin Moncada}\b0 {\super
\fs16\up3\cf0\f0\charscalex100\b {1}\b0 }\par\pard\li1080\ri0\sl-386\slmult0 \f
s12\cf0\f0\charscalex100\i {1}\i0 { }\fs16\cf0\f0\charscalex100\i {Department of
Dermatology, Hospital Central, Universidad Aut}\i0 \fs16\cf0\f0\charscalex100\i
{}\i0 \fs16\cf0\f0\charscalex100\i {onoma de San Luis Potos}\i0 \fs16\cf0\f0\cha
rscalex100\i {}\i0 \fs16\cf0\f0\charscalex100\i {\uc1\u305X, San Luis Potos}\i0 \
fs16\cf0\f0\charscalex100\i {}\i0 \fs16\cf0\f0\charscalex100\i {\uc1\u305X, Mexic
o}\i0 \par\pard\li1080\ri0\sl-213\slmult0 \fs12\cf0\f0\charscalex100\i {2}\i0 {
}\fs16\cf0\f0\charscalex100\i {Department of Dermatology, Hospital Central \uc1\
u8220XDr. Ignacio Morones Prieto\uc1\u8221X, 2395 Venustiano Carranza Avenue, CP
78210,}\i0 \par\pard\li1160\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100\i {Sa
n Luis Potos}\i0 \fs16\cf0\f0\charscalex100\i {}\i0 \fs16\cf0\f0\charscalex100\i
{\uc1\u305X, SLP, Mexico}\i0 \par\pard\li1080\ri0\sl-213\slmult0 \fs12\cf0\f0\ch
arscalex100\i {3}\i0 { }\fs16\cf0\f0\charscalex100\i {Department of Pathology, H
ospital Central, Universidad Aut}\i0 \fs16\cf0\f0\charscalex100\i {}\i0 \fs16\cf0
\f0\charscalex100\i {onoma de San Luis Potos}\i0 \fs16\cf0\f0\charscalex100\i {}\
i0 \fs16\cf0\f0\charscalex100\i {\uc1\u305X, San Luis Potos}\i0 \fs16\cf0\f0\cha
rscalex100\i {}\i0 \fs16\cf0\f0\charscalex100\i {\uc1\u305X, SLP, Mexico}\i0 \par
\pard\li1080\ri0\sl-200\slmult0 \fs12\cf0\f0\charscalex100\i {4}\i0 { }\fs16\cf0
\f0\charscalex100\i {Coordinaci}\i0 \fs16\cf0\f0\charscalex100\i {}\i0 \fs16\cf0\
f0\charscalex100\i {on para la Innovaci}\i0 \fs16\cf0\f0\charscalex100\i {}\i0 \f
s16\cf0\f0\charscalex100\i {on y la Aplicaci}\i0 \fs16\cf0\f0\charscalex100\i {}\

i0 \fs16\cf0\f0\charscalex100\i {on de la Ciencia y la Tecnolog}\i0 \fs16\cf0\f0
\charscalex100\i {}\i0 \fs16\cf0\f0\charscalex100\i {\uc1\u305Xa, Universidad Aut
}\i0 \fs16\cf0\f0\charscalex100\i {}\i0 \fs16\cf0\f0\charscalex100\i {onoma de Sa
n Luis Potos}\i0 \fs16\cf0\f0\charscalex100\i {}\i0 \fs16\cf0\f0\charscalex100\i
{\uc1\u305X,}\i0 \par\pard\li1160\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100\
i {San Luis Potos}\i0 \fs16\cf0\f0\charscalex100\i {}\i0 \fs16\cf0\f0\charscalex1
00\i {\uc1\u305X, SLP, Mexico}\i0 \par\pard\li1066\ri0\sl-373\slmult0 \fs16\cf0\
f0\charscalex100 {Correspondence should be addressed to Bertha Torres- }\fs16\cf
0\f0\charscalex100 {}\fs16\cf0\f0\charscalex100 {Alvarez, }\fs16\cf0\f0\charscale
x100 {torresmab@yahoo.com.mx}\par\pard\li1066\ri0\sl-360\slmult0 \fs18\cf0\f0\ch
arscalex100 {Received 16 January 2011; Revised 16 May 2011; Accepted 8 June 2011
}\par\pard\li1066\ri0\sl-360\slmult0 \fs18\cf0\f0\charscalex100 {Academic Editor
: D. J. Tobin}\par\pard\li1066\ri0\sl-373\slmult0 \fs18\cf0\f0\charscalex100 {Co
pyright 2011 Jose\uc1\u64257Xna Navarrete-Sol}\fs18\cf0\f0\charscalex100 {}\fs18\
cf0\f0\charscalex100 {\uc1\u305Xs et al. This is an open access article distribu
ted under the Creative Commons Attribution}\par\pard\li1066\ri0\sl-213\slmult0 \
fs16\cf0\f0\charscalex100 {License, which permits unrestricted use, distribution
, and repro}\fs16\cf0\f0\charscalex100 {duction in any medium, provided the orig
inal work is properly}\par\pard\li1066\ri0\sl-200\slmult0 \fs18\cf0\f0\charscale
x100 {cited.}\par\pard\li1066\ri0\sl-386\slmult0 \fs14\cf0\f0\charscalex100\i {B
ackground}\i0 \fs16\cf0\f0\charscalex100 {. Multiple modalities have been used i
n the treatment of melasma with variable success. Niacinamide has anti-}\par\par
d\li1066\ri0\sl-226\slmult0 \fs16\cf0\f0\charscalex100 {in\uc1\u64258Xammatory p
roperties and is able to decrease the transfer of melanosomes.}{ }\fs16\cf0\f0\c
harscalex100\i {Objective}\i0 \fs16\cf0\f0\charscalex100 {. To evaluate the ther
apeutic e}\fs16\cf0\f0\charscalex100 {\uc1\u64256X}\fs16\cf0\f0\charscalex100 {e
ct of}\par\pard\li1066\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {topical ni
acinamide versus hydroquinone (HQ) in melasma patients.}{ }\fs14\cf0\f0\charscal
ex100\i {Patients and Methods}\i0 \fs16\cf0\f0\charscalex100 {. Twenty-seven mel
asma patients were}\par\pard\li1066\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex10
0 {randomized to receive for eight weeks 4% niacinamide cream on one side of the
face, and 4% HQ cream on the other. Sunscreen}\par\pard\li1066\ri0\sl-200\slmul
t0 \fs14\cf0\f0\charscalex100 {was applied along the observation period. They we
re assessed by noninvasive techniques for the evaluation of skin color, as well
as}\par\pard\li1066\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {subjective sc
ales and histological sections initially and after the treatment with niacinamid
e.}{ }\fs16\cf0\f0\charscalex100\i {Results}\i0 \fs16\cf0\f0\charscalex100 {. Al
l patients showed pigment}\par\pard\li1066\ri0\sl-226\slmult0 \fs16\cf0\f0\chars
calex100 {improvement with both treatments. Colorimetric measures did not show s
tatistical di}\fs16\cf0\f0\charscalex100 {\uc1\u64256X}\fs14\cf0\f0\charscalex10
0 {erences between both sides. However, good}\par\pard\li1066\ri0\sl-200\slmult0
\fs16\cf0\f0\charscalex100 {to excellent improvement was observed with niacinam
ide in 44% of patients, compared to 55% with HQ. Niacinamide reduced}\par\pard\l
i1066\ri0\sl-226\slmult0 \fs16\cf0\f0\charscalex100 {importantly the mast cell i
n\uc1\u64257Xltrate and showed improvement of solar elastosis in melasma skin. S
ide e}\fs16\cf0\f0\charscalex100 {\uc1\u64256X}\fs16\cf0\f0\charscalex100 {ects
were present in 18%}\par\pard\li1066\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex1
00 {with niacinamide versus 29% with HQ.}{ }\fs14\cf0\f0\charscalex100\i {Conclu
sion}\i0 \fs16\cf0\f0\charscalex100 {. Niacinamide induces a decrease in pigment
ation, in\uc1\u64258Xammatory in\uc1\u64257Xltrate, and}\par\pard\li1066\ri0\sl226\slmult0 \fs18\cf0\f0\charscalex100 {solar elastosis. Niacinamide is a safe a
nd e}\fs18\cf0\f0\charscalex100 {\uc1\u64256X}\fs18\cf0\f0\charscalex100 {ective
therapeutic agent for this condition.}\par\pard\sect\sectd\sbknone\cols2\colno1
\colw5506\colsr-0\colno2\colw5693\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pa
rd\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf
0\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-213\slmult0
\fs18\cf0\par\pard\li346\ri0\sl-346\slmult0 \fs24\cf0\f0\charscalex100\b {1. Int
roduction}\b0 \par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl
-213\slmult0 \fs20\cf0\f0\charscalex100 {Melasma is de\uc1\u64257Xned as an acqu
ired chronic hypermelanosis}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\char

scalex100 {on sun exposed areas being most frequently found in}\par\pard\li346\r
i0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {women with III-V phototypes of Fit
zpatrick. The etiology is}\par\pard\li346\ri0\sl-240\slmult0 \fs18\cf0\f0\charsc
alex100 {not completely elucidated; however, the ultraviolet sunlight}\par\pard\
li346\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {exposure appears to be the
most signi\uc1\u64257Xcant factor [}\fs18\cf0\f0\charscalex100 {1}\fs18\cf0\f0\c
harscalex100 {]. The}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex1
00 {basis of the treatment is photoprotection. Diverse modalities}\par\pard\li34
6\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {in drug therapy have been used
such as hydroquinone (HQ),}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\chars
calex100 {which inhibits the tyrosinase enzyme activity. In spite of}\par\pard\l
i346\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {its serious adverse e}\fs18\
cf0\f0\charscalex100 {\uc1\u64256X}\fs18\cf0\f0\charscalex100 {ects and moderate
results in 80% of}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li
0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\par
d\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par
\pard\li0\ri0\sl-333\slmult0 \fs20\cf0\f0\charscalex100 {patients, HQ is conside
red the gold standard treatment in}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0
\charscalex100 {melasma although usually relapses after suspension [}\fs20\cf0\f
0\charscalex100 {2}\fs20\cf0\f0\charscalex100 {].}\par\pard\li293\ri0\sl-226\slm
ult0 \fs18\cf0\f0\charscalex100 {Niacinamide studies have demonstrated a suppres
sion of}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {melanosome
transfer suggesting the reduction of cutaneous}\par\pard\li0\ri0\sl-226\slmult0
\fs20\cf0\f0\charscalex100 {pigmentation [}\fs20\cf0\f0\charscalex100 {3}\fs20\c
f0\f0\charscalex100 {], but to date there has been no clinical}\par\pard\li0\ri0
\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {report of this e}\fs20\cf0\f0\charsc
alex100 {\uc1\u64256X}\fs20\cf0\f0\charscalex100 {ect in melasma. There have bee
n several}\par\pard\li0\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {reports r
egarding other bene\uc1\u64257Xcial e}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\
fs20\cf0\f0\charscalex100 {ects of topical niaci-}\par\pard\li0\ri0\sl-186\slmul
t0 \fs20\cf0\f0\charscalex100 {namide on the skin, including prevention of photo
immuno-}\par\pard\li0\ri0\sl-213\slmult0 \fs20\cf0\f0\charscalex100 {suppression
and photocarcinogenesis [}\fs20\cf0\f0\charscalex100 {4}\fs20\cf0\f0\charscalex
100 {], anti-in\uc1\u64258Xammatory}\par\pard\li0\ri0\sl-253\slmult0 \fs20\cf0\f
0\charscalex100 {e}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\charsca
lex100 {ects in acne [}\fs20\cf0\f0\charscalex100 {5}\fs20\cf0\f0\charscalex100
{], rosacea [}\fs20\cf0\f0\charscalex100 {6}\fs20\cf0\f0\charscalex100 {], and p
soriasis [}\fs20\cf0\f0\charscalex100 {7}\fs20\cf0\f0\charscalex100 {]. It also}
\par\pard\li0\ri0\sl-200\slmult0 \fs20\cf0\f0\charscalex100 {increases biosynthe
sis of ceramides, as well as other stratum}\par\pard\sect\sectd\sbknone\pard\sec
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fs18\cf0\f0\charscalex100 {Figure}{ }\fs18\cf0\f0\charscalex100 {1: Right side t
reated with niacinamide. View at onset and 8 weeks later with an excellent decre
ase in pigmentation.}\par\pard\li2013\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li20
\pard\li2013\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li2013\ri0\sl-213\slmult0 \fs
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f0\charscalex100 {2: Left side treated with HQ: Onset and 8 weeks later with an
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i346\ri0\sl-320\slmult0 \fs20\cf0\f0\charscalex100 {corneum lipids with enhanced
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rscalex100 {rier function [}\fs20\cf0\f0\charscalex100 {8}\fs20\cf0\f0\charscale
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cf0\f0\charscalex100 {demonstrated in randomized trials [}\fs20\cf0\f0\charscale
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cf0\f0\charscalex100 {The guidelines to clinical trials in melasma have sug-}\pa
r\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {gested a correct dia
gnosis by using at least two subjective}\par\pard\li346\ri0\sl-226\slmult0 \fs20
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\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {the therapeutic g
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arscalex100 {].}\par\pard\li653\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {T
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hods}\b0 \par\pard\li346\ri0\sl-386\slmult0 \fs20\cf0\f0\charscalex100 {This is
a double-blind, left-right randomized clinical trial.}\par\pard\li346\ri0\sl-226
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he ethic}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {committe
e in our hospital, and each subject signed a written}\par\pard\li346\ri0\sl-226\
slmult0 \fs20\cf0\f0\charscalex100 {informed consent. The sample size was determ
ined based}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl
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0 {on favorable response: 0.8 for HQ and at least 0.4 for}\par\pard\li0\ri0\sl-2
53\slmult0 \fs20\cf0\f0\charscalex100 {niacinamide, with 95% IC, two tails,}{ }\
fs20\cf0\f0\charscalex100\i {\uc1\u945X}\i0 { }\fs20\cf0\f0\charscalex100 {of 0.
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x100 {of 0.8.}\par\pard\li293\ri0\sl-200\slmult0 \fs18\cf0\f0\charscalex100 {We
included 27 women with melasma attending the}\par\pard\li0\ri0\sl-226\slmult0 \f
s20\cf0\f0\charscalex100 {outpatient clinic of Dermatology Department at the Hos
pital}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {Central \uc1\
u8220XDr. Ignacio Morones Prieto\uc1\u8221X, from March 2008 to}\par\pard\li0\ri
0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {February 2009.}\par\pard\li293\ri0\
sl-226\slmult0 \fs18\cf0\f0\charscalex100 {Our inclusion criteria were women at
least 18 years old}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {
without any topical, systemic, laser, and surgical treatment}\par\pard\li0\ri0\s
l-226\slmult0 \fs20\cf0\f0\charscalex100 {on face during the previous year. The
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colno3\colw280\colsr-0\colno4\colw706\colsr-0\colno5\colw266\colsr-0\colno6\colw
720\colsr-0\colno7\colw280\colsr-0\colno8\colw706\colsr-0\colno9\colw266\colsr-0
\colno10\colw1493\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346
\ri0\sl-360\slmult0 \fs20\cf0\f0\charscalex100 {not photoexposed skin; these wer
e stained with haematoxylin}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\char
scalex100 {and eosin to determine the general histopathological features}\par\pa
rd\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {of the epidermis and der
mis.}\par\pard\li653\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {The in\uc1\u
64258Xammatory in\uc1\u64257Xltrate was counted manually by}\par\pard\li346\ri0\
sl-253\slmult0 \fs20\cf0\f0\charscalex100 {two independent blinded observers, us
ing a 0}\fs20\cf0\f0\charscalex100\i {.}\i0 \fs20\cf0\f0\charscalex100 {5}{ }\fs
18\cf0\f0\charscalex100 {}{ }\fs20\cf0\f0\charscalex100 {0}\fs20\cf0\f0\charscale
x100\i {.}\i0 \fs20\cf0\f0\charscalex100 {5 mm}\par\pard\li346\ri0\sl-226\slmult
0 \fs18\cf0\f0\charscalex100 {ocular grid and 100}\fs16\cf0\f0\charscalex100 {}{
}\fs18\cf0\f0\charscalex100 {magni\uc1\u64257Xcation. The cells were counted}\pa
r\pard\li346\ri0\sl-200\slmult0 \fs20\cf0\f0\charscalex100 {for the entire secti
on, and the results expressed as the number}\par\pard\li346\ri0\sl-226\slmult0 \
fs18\cf0\f0\charscalex100 {of cells per mm}{\super \fs12\up2\cf0\f0\charscalex10
0 {2}}\fs18\cf0\f0\charscalex100 {. The same procedure was employed to count}\pa
r\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {melanocytes (Fontana
Masson) and metachromatic granules}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0
\f0\charscalex100 {(Wright-Giemsa) in mast cells. To count the epidermal}\par\pa
rd\li346\ri0\sl-240\slmult0 \*\tx4440\fs20\cf0\f0\charscalex100 {melanin, we obt
ained a magni\uc1\u64257Xcation of 40}\fs18\cf0\f0\charscalex100 {}\tab \fs20\cf0
\f0\charscalex100 {to get a}\par\pard\li346\ri0\sl-213\slmult0 \fs20\cf0\f0\char
scalex100 {scanning view of the epidermis. Images were obtained from}\par\column
\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0
\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-320\slmult0 \fs16
\cf0\f0\charscalex100 {10}\par\pard\li80\ri0\sl-253\slmult0 \fs14\cf0\f0\charsca
lex100 {9}\par\pard\li80\ri0\sl-253\slmult0 \fs14\cf0\f0\charscalex100 {8}\par\p
ard\li80\ri0\sl-253\slmult0 \fs14\cf0\f0\charscalex100 {7}\par\pard\li80\ri0\sl253\slmult0 \fs14\cf0\f0\charscalex100 {6}\par\pard\li80\ri0\sl-253\slmult0 \fs1
4\cf0\f0\charscalex100 {5}\par\pard\li80\ri0\sl-253\slmult0 \fs14\cf0\f0\charsca
lex100 {4}\par\pard\li80\ri0\sl-253\slmult0 \fs14\cf0\f0\charscalex100 {3}\par\p
ard\li80\ri0\sl-253\slmult0 \fs14\cf0\f0\charscalex100 {2}\par\pard\li80\ri0\sl253\slmult0 \fs14\cf0\f0\charscalex100 {1}\par\pard\li80\ri0\sl-253\slmult0 \fs1
4\cf0\f0\charscalex100 {0}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\
pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\
par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\
cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \f
s18\cf0\par\pard\li0\ri0\sl-346\slmult0 \fs16\cf0\f0\charscalex100 {6}\par\colum
n\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf
0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs1
8\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-280\slmult0
\fs16\cf0\f0\charscalex100 {8}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\
s18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult
0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-160\sl
mult0 \fs16\cf0\f0\charscalex100 {6}\par\column\pard\li0\ri0\sl-213\slmult0 \fs1
8\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0
\fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmu
lt0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-333\
slmult0 \fs16\cf0\f0\charscalex100 {7}\par\column\pard\li0\ri0\sl-213\slmult0 \f
mult0 \fs18\cf0\par\pard\li0\ri0\sl-306\slmult0 \fs16\cf0\f0\charscalex100 {8}\p
ar\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0
lt0 \fs18\cf0\par\pard\li0\ri0\sl-253\slmult0 \fs16\cf0\f0\charscalex100 {9}\par

\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \f
mult0 \fs18\cf0\par\pard\li0\ri0\sl-320\slmult0 \fs16\cf0\f0\charscalex100 {7}\p
ar\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0
slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0
\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0
\ri0\sl-280\slmult0 \fs16\cf0\f0\charscalex100 {3}\par\pard\sect\sectd\sbknone\p
gwsxn12000\pghsxn15840\marglsxn666\margrsxn133\cols5\colno1\colw6360\colsr-0\col
no2\colw973\colsr-0\colno3\colw1106\colsr-0\colno4\colw866\colsr-0\colno5\colw18
93\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {the entire 2 mm sam
ple with a digital camera mounted}\par\pard\li346\ri0\sl-240\slmult0 \fs18\cf0\f
0\charscalex100 {on a microscope (Olympus CX 31) which was connected}\par\pard\l
i346\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {to a personal computer (PC).
The image signals taken by}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\char
scalex100 {the PC were evaluated using Image-Pro Plus Version 4.5}\par\pard\li34
6\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {(Media Cybernetics, Silver Spri
ng, MA, USA). With the aim}\par\column\pard\li146\ri0\sl-186\slmult0 \fs16\cf0\f
0\charscalex100 {Mild}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri
0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-186\slmult0 \fs14\cf0\f0\charscal
ex100 {Hydroquinone}\par\pard\li0\ri0\sl-266\slmult0 \fs16\cf0\f0\charscalex100
{Niacinamide}\par\column\pard\li0\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100
{Moderate}\par\column\pard\li0\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {Go
od}\par\column\pard\li0\ri0\sl-186\slmult0 \fs16\cf0\f0\charscalex100 {Excellent
}\par\pard\sect\sectd\sbknone\pgwsxn12000\pghsxn15840\marglsxn666\margrsxn133\co
ls2\colno1\colw5506\colsr-0\colno2\colw5693\pard\li346\ri0\sl-226\slmult0 \fs18\
cf0\f0\charscalex100 {of discern possible abnormalities of melanin in melasma}\p
ar\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {patients as shown b
efore [}\fs18\cf0\f0\charscalex100 {11}\fs18\cf0\f0\charscalex100 {], or even be
ing induced by the}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100
{intervention, we perform a qualitative analysis by Raman}\par\pard\li346\ri0\s
l-226\slmult0 \fs18\cf0\f0\charscalex100 {spectrophotometry (Horiba, Jobin-Yvon
T64000. Edison,}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {N
J, USA) before and at the conclusion of the study.}\par\pard\li653\ri0\sl-226\sl
mult0 \fs20\cf0\f0\charscalex100 {Patients were randomized in a double-blind man
ner to}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {receive on
e treatment on the left and the other on the}\par\pard\li346\ri0\sl-226\slmult0
\fs20\cf0\f0\charscalex100 {right side of the face. They received two containers
labeled}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {right or
left with 4% niacinamide (Nicomide-T cream 4%,}\par\pard\li346\ri0\sl-226\slmul
t0 \fs20\cf0\f0\charscalex100 {DUSA Pharmaceuticals Inc.) or 4% HQ (Eldoquin cre
am}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {4%, Valeant Ph
armaceutical). All patients were instructed to}\par\pard\li346\ri0\sl-226\slmult
0 \fs20\cf0\f0\charscalex100 {apply the correct amount of both treatments and to
use a}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {SPF 50+ br
oad spectrum sunscreen every 3 hours during day}\par\pard\li346\ri0\sl-226\slmul
t0 \fs20\cf0\f0\charscalex100 {time.}\par\pard\li653\ri0\sl-226\slmult0 \fs18\cf
0\f0\charscalex100 {Concomitant use of other skin care products or systemic}\par
\pard\li346\ri0\sl-240\slmult0 \fs20\cf0\f0\charscalex100 {treatments was not al
lowed during the study. Treatment}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f
0\charscalex100 {was administered for the period of 8 weeks, with basal}\par\par
d\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {evaluation and followup a
t 4 and 8 weeks. Assessments}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\cha
rscalex100 {included a skin pigment evaluation by a chromameter (CR-}\par\pard\l
i346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {300; Minolta, Osaka, Japan),
melasma area and severity index}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0
\charscalex100 {(MASI), physician global assessment (PGA) by an inde-}\par\pard\

li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {pendent observer, conventio
nal photography, and infrared}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\ch
arscalex100 {thermography (Flexcam S, Infrared solutions, USA) with}\par\pard\li
346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {photographic register which m
ainly was used to detect irri-}\par\pard\li346\ri0\sl-253\slmult0 \fs20\cf0\f0\c
harscalex100 {tation. All side-e}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\
cf0\f0\charscalex100 {ects were registered. The double-blinded}\par\pard\li346\r
i0\sl-200\slmult0 \fs20\cf0\f0\charscalex100 {study was opened at 8 weeks in ord
er to take a 2 mm biopsy}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charsca
lex100 {in the side treated with niacinamide.}\par\pard\li653\ri0\sl-253\slmult0
\fs18\cf0\f0\charscalex100 {For statistical analysis, we used the Student}{ }\f
s18\cf0\f0\charscalex100\i {t}\i0 \fs18\cf0\f0\charscalex100 {-test and}{ }\fs18
\cf0\f0\charscalex100\i {X}\i0 \fs12\cf0\f0\charscalex100 {2}{\sub \fs18\cf0\f0\
charscalex100 {,}}\par\pard\li346\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100
{and a}{ }\fs20\cf0\f0\charscalex100\i {P}\i0 { }\fs20\cf0\f0\charscalex100 {val
ue of less than 0.05 was considered signi\uc1\u64257Xcant.}\par\pard\li346\ri0\s
l-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-266\slmult0 \fs24\cf0\f0\charscale
x100\b {3. Results}\b0 \par\pard\li346\ri0\sl-386\slmult0 \fs20\cf0\f0\charscale
x100 {Twenty-seven female patients with melasma were included,}\par\pard\li346\r
i0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {12 (33%) were of skin phototype IV
, and 13 (48%) of type V.}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charsc
alex100 {The pattern of melasma was centrofacial in 13 (50%), malar}\par\pard\li
346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {in 10 (37%), and mandibular i
n 4 (14%).}\par\pard\li653\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {The pa
tients age ranged from 25 to 53 years (mean, 37}\par\pard\li346\ri0\sl-226\slmul
t0 \fs20\cf0\f0\charscalex100 {years). The duration of melasma varied from 4 to
8 years}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {(mean, 6.
5 years). Family history of melasma was found in}\par\pard\li346\ri0\sl-226\slmu
lt0 \fs20\cf0\f0\charscalex100 {19 (70%) patients. The most frequent precipitati
ng factor}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {was the
sun exposure followed by pregnancy. Eight patients}\par\pard\li346\ri0\sl-226\s
lmult0 \fs20\cf0\f0\charscalex100 {(29%) have used oral contraceptives.}\par\col
umn\pard\li0\ri0\sl-266\slmult0 \fs18\cf0\f0\charscalex100 {Figure}{ }\fs18\cf0\
f0\charscalex100 {3: Physicians Global Assessment in melasma patients with}\par\
pard\li0\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {niacinamide versus HQ.}\
cf0\par\pard\li0\ri0\sl-360\slmult0 \*\tx1800\fs20\cf0\f0\charscalex100\i {3.1.
Clinical Results.}\i0 \tab \fs20\cf0\f0\charscalex100 {The onset average MASI sc
ore for}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {the HQ side
was 4 (5% CI, 90.9\uc1\u8211X1.8) and 1.2 (95% IC,}\par\pard\li0\ri0\sl-253\slm
ult0 \*\tx2760\fs20\cf0\f0\charscalex100 {0.8\uc1\u8211X1.6) after eight weeks (
}\fs20\cf0\f0\charscalex100\i {P <}\i0 \tab \fs20\cf0\f0\charscalex100 {0}\fs20\
cf0\f0\charscalex100\i {.}\i0 \fs20\cf0\f0\charscalex100 {001). The initial MASI
}\par\pard\li0\ri0\sl-213\slmult0 \fs20\cf0\f0\charscalex100 {score for the niac
inamide side was 3.7 (95% CI, 2.9\uc1\u8211X}\par\pard\li0\ri0\sl-226\slmult0 \f
s20\cf0\f0\charscalex100 {4.4) and 1.4 (95% CI, 3.3\uc1\u8211X4.7) at the end of
the study}\par\pard\li0\ri0\sl-253\slmult0 \*\tx546\fs20\cf0\f0\charscalex100 {
(}\fs20\cf0\f0\charscalex100\i {P <}\i0 \tab \fs20\cf0\f0\charscalex100 {0}\fs20
\cf0\f0\charscalex100\i {.}\i0 \fs20\cf0\f0\charscalex100 {001). The average dec
rease for HQ was 70% and}\par\pard\li0\ri0\sl-200\slmult0 \fs20\cf0\f0\charscale
x100 {62% for niacinamide. This improvement was registered}\par\pard\li0\ri0\sl226\slmult0 \fs20\cf0\f0\charscalex100 {using conventional photography (Figures
}\fs20\cf0\f0\charscalex100 {1 }\fs20\cf0\f0\charscalex100 {and }\fs20\cf0\f0\ch
arscalex100 {2}\fs20\cf0\f0\charscalex100 {) with no}\par\pard\li0\ri0\sl-253\sl
mult0 \fs20\cf0\f0\charscalex100 {perceptible di}\fs20\cf0\f0\charscalex100 {\uc
1\u64256X}\fs20\cf0\f0\charscalex100 {erences between both sides.}\par\pard\li29
3\ri0\sl-200\slmult0 \fs20\cf0\f0\charscalex100 {The PGA rated the niacinamide s
ide improvement as}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {
excellent in three patients, good in nine, moderate in seven,}\par\pard\li0\ri0\
sl-226\slmult0 \fs20\cf0\f0\charscalex100 {and mild in eight. The HQ-treated sid

e was rated excellent}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex10
0 {in seven, good in eight, moderate in six, and mild in six}\par\pard\li0\ri0\s
l-226\slmult0 \fs20\cf0\f0\charscalex100 {patients (}\fs20\cf0\f0\charscalex100
{Figure 3). Data showed statistical signi\uc1\u64257Xcance for}\par\pard\li0\ri0
\sl-253\slmult0 \*\tx2080\*\tx2320\*\tx4666\fs20\cf0\f0\charscalex100 {both trea
tments, HQ (}\fs20\cf0\f0\charscalex100\i {P}\i0 \tab \fs18\cf0\f0\charscalex100
{=}\tab \fs20\cf0\f0\charscalex100 {0}\fs20\cf0\f0\charscalex100\i {.}\i0 \fs20
\cf0\f0\charscalex100 {003), and niacinamide (}\fs20\cf0\f0\charscalex100\i {P}\
i0 \tab \fs18\cf0\f0\charscalex100 {=}\par\pard\li0\ri0\sl-253\slmult0 \fs20\cf0
\f0\charscalex100 {0}\fs20\cf0\f0\charscalex100\i {.}\i0 \fs20\cf0\f0\charscalex
100 {005).}\par\pard\li293\ri0\sl-186\slmult0 \fs20\cf0\f0\charscalex100 {Colori
metric assessment was performed initially and at}\par\pard\li0\ri0\sl-226\slmult
0 \fs20\cf0\f0\charscalex100 {the end of the study; we evaluated the luminosity
axis (L}\fs12\cf0\f0\charscalex100 {\uc1\u8727X}\fs20\cf0\f0\charscalex100 {)}\p
ar\pard\li0\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {as well as the erythe
ma axis (a}\fs12\cf0\f0\charscalex100 {\uc1\u8727X}\fs20\cf0\f0\charscalex100 {)
. The lightening e}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\charsca
lex100 {ect of}\par\pard\li0\ri0\sl-186\slmult0 \fs20\cf0\f0\charscalex100 {HQ a
nd niacinamide was apparent at 4 weeks of treatment,}\par\pard\li0\ri0\sl-226\sl
mult0 \fs20\cf0\f0\charscalex100 {whereas it was more evident at 8 weeks. Colori
metric}\par\pard\li0\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {measures sho
wed no statistical di}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\char
scalex100 {erences between both}\par\pard\li0\ri0\sl-213\slmult0 \fs20\cf0\f0\ch
arscalex100 {treatments (}\fs20\cf0\f0\charscalex100 {Table 1}\fs20\cf0\f0\chars
calex100 {). The erythema was more intense on}\par\pard\li0\ri0\sl-226\slmult0 \
fs20\cf0\f0\charscalex100 {the side treated with HQ than with niacinamide, but i
t was}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {not statistic
ally signi\uc1\u64257Xcative. Infrared light thermography at}\par\pard\li0\ri0\s
l-240\slmult0 \fs20\cf0\f0\charscalex100 {environmental temperature of 21}\fs12\
cf0\f0\charscalex100 {\uc1\u9702X}{ }\fs20\cf0\f0\charscalex100 {C showed a dimi
nished}\par\pard\li0\ri0\sl-240\slmult0 \fs20\cf0\f0\charscalex100 {temperature
of 0.8}\fs12\cf0\f0\charscalex100 {\uc1\u9702X}\fs20\cf0\f0\charscalex100 {C in
both sides after treatment. There was}\par\pard\li0\ri0\sl-253\slmult0 \fs20\cf0
\f0\charscalex100 {no statistical di}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\f
s20\cf0\f0\charscalex100 {erence between both treatments.}\par\pard\li0\ri0\sl-2
13\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-280\slmult0 \*\tx2226\fs18\cf0\f0\chars
calex100\i {3.2. Histopathology Results.}\i0 \tab \fs20\cf0\f0\charscalex100 {Th
e biopsy samples were stained}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\char
scalex100 {with haematoxylin and eosin for general histology, Fontana}\par\pard\
li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {Masson to evaluate melanin pi
gment, and Wright-Giemsa}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscale
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r\pard\li0\ri0\sl-200\slmult0 \fs16\cf0\f0\charscalex100 {(b)}\par\pard\sect\sec
td\sbknone\pgwsxn12000\pghsxn15840\marglsxn666\margrsxn133\pard\li346\ri0\sl-386
\slmult0 \*\tx946\fs18\cf0\f0\charscalex100 {Figure}\tab \fs18\cf0\f0\charscalex
100 {4: Epidermal pigmentation reduction. (a) Basal melasma skin biopsy, (b) ski
n biopsy posttreated with niacinamide. (Fontana}\par\pard\li346\ri0\sl-213\slmul
t0 \fs18\cf0\f0\charscalex100 {Masson, original magni\uc1\u64257Xcation 40x). Be

low is shown the measured posi}\fs18\cf0\f0\charscalex100 {tive areas for melani
n using a computer-assisted image analysis}\par\pard\li346\ri0\sl-200\slmult0 \f
s18\cf0\f0\charscalex100 {program.}\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\
par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-213\slmult0 \f
s18\cf0\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {Table}{ }\
fs18\cf0\f0\charscalex100 {1: Changes in MASI scores and colorimetric values for
4% HQ and 4% niacinamide-treated sides in 27 patients with melasma. Mast}\par\p
ard\li346\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {cell counts and melanin
expression initially and after treatment with niacinamide in 11 patients.}\par\
pard\sect\sectd\sbknone\pgwsxn12000\pghsxn15840\marglsxn666\margrsxn133\cols7\co
lno1\colw4013\colsr-0\colno2\colw293\colsr-0\colno3\colw1373\colsr-0\colno4\colw
1160\colsr-0\colno5\colw1066\colsr-0\colno6\colw2066\colsr-0\colno7\colw1226\par
d\li2666\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li2666\ri0\sl-213\slmult0 \fs18\c
f0\par\pard\li2666\ri0\sl-200\slmult0 \fs18\cf0\f0\charscalex100 {Onset}\par\col
umn\pard\li0\ri0\sl-373\slmult0 \fs18\cf0\f0\charscalex100 {HQ}\par\column\pard\
li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\p
ard\li0\ri0\sl-200\slmult0 \fs18\cf0\f0\charscalex100 {8 wk}\par\column\pard\li0
\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-413\slmult0 \fs18\cf0\f0\chars
calex100\i {P}\i0 \par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0
\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-200\slmult0 \fs18\cf0\f0\chars
calex100 {Onset}\par\column\pard\li0\ri0\sl-373\slmult0 \fs18\cf0\f0\charscalex1
00 {Niacinamide}\par\pard\li640\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {8
wk}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-413\sl
mult0 \fs18\cf0\f0\charscalex100\i {P}\i0 \par\pard\sect\sectd\sbknone\pgwsxn120
00\pghsxn15840\marglsxn666\margrsxn133\cols7\colno1\colw2293\colsr-0\colno2\colw
1653\colsr-0\colno3\colw1533\colsr-0\colno4\colw986\colsr-0\colno5\colw1653\cols
r-0\colno6\colw1653\colsr-0\colno7\colw1426\pard\li386\ri0\sl-253\slmult0 \fs18\
cf0\f0\charscalex100 {MASI}\par\pard\li386\ri0\sl-253\slmult0 \*\tx613\fs18\cf0\
f0\charscalex100 {L}\fs10\cf0\f0\charscalex100 {\uc1\u8727X}\tab \fs18\cf0\f0\ch
arscalex100 {axis}\par\pard\li386\ri0\sl-240\slmult0 \*\tx600\fs18\cf0\f0\charsc
alex100 {a}\fs10\cf0\f0\charscalex100 {\uc1\u8727X}\tab \fs18\cf0\f0\charscalex1
00 {axis}\par\pard\li386\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {Mast cel
ls/mm}\fs12\cf0\f0\charscalex100 {2}\par\pard\li386\ri0\sl-253\slmult0 \fs18\cf0
\f0\charscalex100 {Stained Melanin (%)}\par\column\pard\li240\ri0\sl-253\slmult0
\fs18\cf0\f0\charscalex100 {4 (.9\uc1\u8211X1.8)}\par\pard\li0\ri0\sl-253\slmul
t0 \fs18\cf0\f0\charscalex100 {50.9 (49.1\uc1\u8211X52.6)}\par\pard\li0\ri0\sl-2
40\slmult0 \fs18\cf0\f0\charscalex100 {12.9 (12.3\uc1\u8211X13.5)}\par\pard\li49
3\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {\uc1\u8212X}\par\pard\li493\ri0
\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {\uc1\u8212X}\par\column\pard\li120\r
i0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {1.2 (.8\uc1\u8211X1.6)}\par\pard\l
i0\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {56 (54.6\uc1\u8211X57.4)}\par\
pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {13.6 (12.6\uc1\u8211X14)
}\par\pard\li440\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {\uc1\u8212X}\par
\pard\li440\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {\uc1\u8212X}\par\colu
mn\pard\li0\ri0\sl-266\slmult0 \fs18\cf0\f0\charscalex100\i {<}\i0 \fs18\cf0\f0\
charscalex100 {0.001}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100
\i {<}\i0 \fs18\cf0\f0\charscalex100 {0.001}\par\pard\li93\ri0\sl-240\slmult0 \f
s18\cf0\f0\charscalex100 {0.25}\par\pard\li160\ri0\sl-253\slmult0 \fs18\cf0\f0\c
harscalex100 {\uc1\u8212X}\par\pard\li160\ri0\sl-253\slmult0 \fs18\cf0\f0\charsc
alex100 {\uc1\u8212X}\par\column\pard\li120\ri0\sl-253\slmult0 \fs18\cf0\f0\char
scalex100 {3.7 (2.9\uc1\u8211X4.4)}\par\pard\li13\ri0\sl-253\slmult0 \fs18\cf0\f
0\charscalex100 {51.1(49.3\uc1\u8211X52.9)}\par\pard\li0\ri0\sl-240\slmult0 \fs1
8\cf0\f0\charscalex100 {12.8 (12.1\uc1\u8211X13.5)}\par\pard\li66\ri0\sl-253\slm
ult0 \fs18\cf0\f0\charscalex100 {22 (15.1\uc1\u8211X28.9)}\par\pard\li186\ri0\sl
-253\slmult0 \fs18\cf0\f0\charscalex100 {8.7 (8\uc1\u8211X9.5)}\par\column\pard\
li133\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {1.4 (3.3\uc1\u8211X4.7)}\pa
r\pard\li66\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {56 (54.4\uc1\u8211X57
.5)}\par\pard\li0\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {13.6 (12.7\uc1\
u8211X14.5)}\par\pard\li66\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {16.3 (
11\uc1\u8211X21.7)}\par\pard\li186\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100
{6 (5.1\uc1\u8211X6.9)}\par\column\pard\li0\ri0\sl-266\slmult0 \fs18\cf0\f0\cha
rscalex100\i {<}\i0 \fs18\cf0\f0\charscalex100 {0.001}\par\pard\li0\ri0\sl-240\s
lmult0 \fs18\cf0\f0\charscalex100\i {<}\i0 \fs18\cf0\f0\charscalex100 {0.001}\pa
r\pard\li93\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {0.08}\par\pard\li93\r
i0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {0.01}\par\pard\li0\ri0\sl-253\slmu
lt0 \fs18\cf0\f0\charscalex100\i {<}\i0 \fs18\cf0\f0\charscalex100 {0.001}\par\p
ard\sect\sectd\sbknone\pgwsxn12000\pghsxn15840\marglsxn666\margrsxn133\pard\li34
6\ri0\sl-240\slmult0 \fs14\cf0\f0\charscalex100 {MASI score was calculated for e
ach treated half-face.}\par\pard\li346\ri0\sl-213\slmult0 \fs16\cf0\f0\charscale
x100 {No statistical di}\fs16\cf0\f0\charscalex100 {\uc1\u64256X}\fs16\cf0\f0\ch
arscalex100 {erences were found in redness (a}\fs10\cf0\f0\charscalex100 {\uc1\u
8727X}\fs16\cf0\f0\charscalex100 {) for both treatments, before and after.}\par\
pard\li346\ri0\sl-226\slmult0 \fs16\cf0\f0\charscalex100 {Final depigmentation I
mprovement (L}\fs10\cf0\f0\charscalex100 {\uc1\u8727X}\fs16\cf0\f0\charscalex100
{) did not show di}\fs16\cf0\f0\charscalex100 {\uc1\u64256X}\fs16\cf0\f0\charsc
alex100 {erences between both treatments (}\fs16\cf0\f0\charscalex100\i {P}\i0 {
}\fs14\cf0\f0\charscalex100 {=}{ }\fs16\cf0\f0\charscalex100 {0}\fs16\cf0\f0\ch
arscalex100\i {.}\i0 \fs16\cf0\f0\charscalex100 {78). In parenthesis, con\uc1\u6
4257Xdence Interval to 95%.}\par\pard\sect\sectd\sbknone\pgwsxn12000\pghsxn15840
\marglsxn666\margrsxn133\cols2\colno1\colw5506\colsr-0\colno2\colw5693\pard\li34
6\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\p
ard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li346\ri0\sl-333\slmult0 \fs20\c
f0\f0\charscalex100 {also present in all of them and moderate presence of}\par\p
ard\li346\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {mast cells near elastot
ic areas in 11 (40%) patients. With}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0
\f0\charscalex100 {Fontana-Masson stained sections, the amount of melanin}\par\p
ard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {was increased in all ep
idermal layers of melasma skin; we}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\
f0\charscalex100 {observed pigment basal cells protruded into the dermis in 20}\
par\pard\li346\ri0\sl-240\slmult0 \fs18\cf0\f0\charscalex100 {(74%) biopsies as
informed before [}\fs18\cf0\f0\charscalex100 {12]. In the upper dermis,}\par\par
d\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {we found scattered melani
n in 19 (70%) melasma biopsies.}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\
charscalex100 {The features in the biopsies of nonexposed sun skin were}\par\par
d\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {close to normal skin.}\pa
r\pard\li653\ri0\sl-266\slmult0 \fs20\cf0\f0\charscalex100 {After 8 weeks of tre
atment, the blind was opened in order}\par\pard\li346\ri0\sl-240\slmult0 \fs20\c
f0\f0\charscalex100 {to take a biopsy from the side treated with niacinamide. We
}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {obtained 11 post
treatment biopsies for analysis. By means}\par\pard\li346\ri0\sl-226\slmult0 \fs
20\cf0\f0\charscalex100 {of digital analysis of biopsies images, we could observ
e that}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {the amount
of epidermal stained melanin was diminished}\par\pard\li346\ri0\sl-253\slmult0
\*\tx2133\fs20\cf0\f0\charscalex100 {signi\uc1\u64257Xcantly (}\fs20\cf0\f0\char
scalex100\i {P <}\i0 \tab \fs20\cf0\f0\charscalex100 {0}\fs20\cf0\f0\charscalex1
00\i {.}\i0 \fs20\cf0\f0\charscalex100 {0007). The average in\uc1\u64258Xammator
y}\par\column\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmu
slmult0 \fs20\cf0\f0\charscalex100 {in\uc1\u64257Xltrate of mast cells was reduc
ed from 22 to 16 cells/mm}{\super \fs14\up2\cf0\f0\charscalex100 {2}}\par\pard\l
i0\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {(}\fs20\cf0\f0\charscalex100\i
{P}\i0 { }\fs18\cf0\f0\charscalex100 {=}{ }\fs20\cf0\f0\charscalex100 {0}\fs20\
cf0\f0\charscalex100\i {.}\i0 \fs20\cf0\f0\charscalex100 {01). Solar elastosis w
as also reduced, but no statistical}\par\pard\li0\ri0\sl-253\slmult0 \fs20\cf0\f
0\charscalex100 {di}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\charsc
alex100 {erences were present (}\fs20\cf0\f0\charscalex100 {Figure 4}\fs20\cf0\f
0\charscalex100 {).}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\
sl-240\slmult0 \*\tx1933\fs18\cf0\f0\charscalex100\i {3.3. Spectrophotometry.}\i
0 \tab \fs20\cf0\f0\charscalex100 {Raman spectroscopy measurements}\par\pard\li0
\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {showed that the molecular struct

ure of melanin was normal}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscal
ex100 {and remained unaltered after exposure to niacinamide}\par\pard\li0\ri0\sl
-226\slmult0 \fs20\cf0\f0\charscalex100 {since the measurements showed the chara
cteristic peaks}\par\pard\li0\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {of
melanin previously published [}\fs20\cf0\f0\charscalex100 {11}\fs20\cf0\f0\chars
calex100 {, }\fs20\cf0\f0\charscalex100 {12}\fs20\cf0\f0\charscalex100 {]. Patie
nts with}\par\pard\li0\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {abnormal m
elanin could respond di}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\ch
arscalex100 {erently to treatment}\par\pard\li0\ri0\sl-200\slmult0 \fs20\cf0\f0\
charscalex100 {and explain the variable success rate to HQ [}\fs20\cf0\f0\charsc
alex100 {11}\fs20\cf0\f0\charscalex100 {]. We wanted}\par\pard\li0\ri0\sl-226\sl
mult0 \fs20\cf0\f0\charscalex100 {to show that these patients were homogeneous i
n this aspect.}\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-32
0\slmult0 \*\tx1333\fs18\cf0\f0\charscalex100\i {3.4. Side E}\i0 \fs20\cf0\f0\ch
arscalex100\i {\uc1\u64256X}\i0 \fs20\cf0\f0\charscalex100\i {ects.}\i0 \tab \fs
20\cf0\f0\charscalex100 {Side e}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\c
f0\f0\charscalex100 {ects were present in the niacinamide}\par\pard\li0\ri0\sl-2
00\slmult0 \fs20\cf0\f0\charscalex100 {side in 5 patients (18%), compared to 8 p
atients (29%)}\par\pard\sect\sectd\sbknone\pgwsxn12000\pghsxn15840\marglsxn666\m
argrsxn133\pard\sect\sectd\sbkpage\pgwsxn12000\pghsxn15840\marglsxn666\margrsxn1
33\margtsxn666\margbsxn240\cols2\colno1\colw5506\colsr-0\colno2\colw5693\pard\li
\cf0\f0\charscalex100 {for the HQ side. The most frequent side e}\fs20\cf0\f0\ch
arscalex100 {\uc1\u64256X}\fs20\cf0\f0\charscalex100 {ects were ery-}\par\pard\l
i346\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {thema, pruritus, and burning
. Most of them were mild for}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\cha
rscalex100 {niacinamide and moderated for HQ. On the niacinamide}\par\pard\li346
\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {side, erythema, pruritus, or bur
ning was present in 2 (7%)}\par\pard\li346\ri0\sl-226\slmult0 \fs18\cf0\f0\chars
calex100 {patients, and on the HQ side they were present in 5}\par\pard\li346\ri
0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {(18%) patients. All these were redu
ced through continuous}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscale
x100 {treatment in both modalities, as the a}\fs12\cf0\f0\charscalex100 {\uc1\u8
727X}{ }\fs20\cf0\f0\charscalex100 {colorimetric value did}\par\pard\li346\ri0\s
l-226\slmult0 \fs20\cf0\f0\charscalex100 {not show signi\uc1\u64257Xcant changes
for both treatments at the end}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\
charscalex100 {of the study.}\par\pard\li346\ri0\sl-213\slmult0 \fs18\cf0\par\pa
rd\li346\ri0\sl-320\slmult0 \fs24\cf0\f0\charscalex100\b {4. Discussion}\b0 \par
\pard\li346\ri0\sl-386\slmult0 \fs20\cf0\f0\charscalex100 {Melasma is a chronic
and persistent hyperpigmentation,}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f
0\charscalex100 {representing a therapeutic challenge because of the high rate}\
par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {of relapses. This
work showed that niacinamide 4% is an}\par\pard\li346\ri0\sl-253\slmult0 \fs20\c
f0\f0\charscalex100 {e}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\cha
rscalex100 {ective agent for the treatment of melasma, as assessed}\par\pard\li3
46\ri0\sl-200\slmult0 \fs20\cf0\f0\charscalex100 {by objective methods and clini
cal evaluation. Our results}\par\pard\li346\ri0\sl-253\slmult0 \fs20\cf0\f0\char
scalex100 {indicate that 4% niacinamide was e}\fs20\cf0\f0\charscalex100 {\uc1\u
64256X}\fs20\cf0\f0\charscalex100 {ective in approximate}\par\pard\li346\ri0\sl200\slmult0 \fs20\cf0\f0\charscalex100 {40% of patients, showing outstanding cli
nical results. In the}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex
100 {posttreatment biopsies, we could observe that the amount of}\par\pard\li346
\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {epidermal melanin and in\uc1\u64
258Xammatory in\uc1\u64257Xltrate was dimin-}\par\pard\li346\ri0\sl-226\slmult0
\fs20\cf0\f0\charscalex100 {ished signi\uc1\u64257Xcantly, as well as solar elas
tosis although it was}\par\pard\li346\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex
100 {not enough to get statistical di}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\
fs20\cf0\f0\charscalex100 {erence. This insu}\fs20\cf0\f0\charscalex100 {\uc1\u6
4259X}\fs20\cf0\f0\charscalex100 {cient}\par\pard\li346\ri0\sl-253\slmult0 \fs20

\cf0\f0\charscalex100 {antiaging e}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs2
0\cf0\f0\charscalex100 {ect could be related to the short time of the}\par\pard\
li346\ri0\sl-186\slmult0 \fs20\cf0\f0\charscalex100 {study; therefore, further c
linical studies using niacinamide}\par\pard\li346\ri0\sl-213\slmult0 \fs20\cf0\f
0\charscalex100 {for longer periods are warranted in this condition. We}\par\par
d\li346\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {observed that the evoluti
on time of melasma did not a}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\
f0\charscalex100 {ect}\par\pard\li346\ri0\sl-213\slmult0 \fs20\cf0\f0\charscalex
100 {the response to treatment. On the other hand, colorimetric}\par\pard\li346\
ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {assessment showed no statistical
di}\fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\charscalex100 {erence b
etween these}\par\pard\li346\ri0\sl-253\slmult0 \*\tx1933\*\tx2173\fs20\cf0\f0\c
harscalex100 {two treatments (}\fs20\cf0\f0\charscalex100\i {P}\i0 \tab \fs18\cf
0\f0\charscalex100 {=}\tab \fs20\cf0\f0\charscalex100 {0}\fs20\cf0\f0\charscalex
100\i {.}\i0 \fs20\cf0\f0\charscalex100 {78). However, the lightening e}\fs20\cf
0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\charscalex100 {ect}\par\pard\li346
\ri0\sl-186\slmult0 \fs20\cf0\f0\charscalex100 {of HQ was evident as early as th
e \uc1\u64257Xrst month of treatment,}\par\pard\li346\ri0\sl-213\slmult0 \fs20\c
f0\f0\charscalex100 {whereas with niacinamide was noted at second month. HQ}\par
\pard\li346\ri0\sl-253\slmult0 \fs18\cf0\f0\charscalex100 {had the disadvantage
of moderate adverse e}\fs18\cf0\f0\charscalex100 {\uc1\u64256X}\fs18\cf0\f0\char
scalex100 {ects in 18%}\par\pard\li346\ri0\sl-200\slmult0 \fs20\cf0\f0\charscale
x100 {of patients, compared to milder in 7% with niacinamide.}\par\pard\li346\ri
0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {Treatment with niacinamide showed n
o signi\uc1\u64257Xcant side}\par\pard\li346\ri0\sl-253\slmult0 \fs18\cf0\f0\cha
rscalex100 {e}\fs18\cf0\f0\charscalex100 {\uc1\u64256X}\fs18\cf0\f0\charscalex10
0 {ects and was well tolerated; therefore, it could be used}\par\pard\li346\ri0\
sl-200\slmult0 \fs20\cf0\f0\charscalex100 {for longer periods, as part of the in
itial hyperpigmentation}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscal
ex100 {treatment and as maintenance drug. However, further trials}\par\pard\li34
6\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {are required to assess the comb
ination of this topical}\par\pard\li346\ri0\sl-253\slmult0 \fs18\cf0\f0\charscal
ex100 {drug with others agents and assess its additive e}\fs18\cf0\f0\charscalex
100 {\uc1\u64256X}\fs18\cf0\f0\charscalex100 {ects in}\par\pard\li346\ri0\sl-200
\slmult0 \fs20\cf0\f0\charscalex100 {the treatment of melasma. The mechanism of
action of}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {niacina
mide in melasma could be through the reduction}\par\pard\li346\ri0\sl-226\slmult
0 \fs20\cf0\f0\charscalex100 {of melanosomes transfer [}\fs20\cf0\f0\charscalex1
00 {3}\fs20\cf0\f0\charscalex100 {], photoprotection actions [}\fs20\cf0\f0\char
scalex100 {4}\fs20\cf0\f0\charscalex100 {],}\par\pard\li346\ri0\sl-226\slmult0 \
fs20\cf0\f0\charscalex100 {its anti-in\uc1\u64258Xammatory properties [}\fs20\cf
0\f0\charscalex100 {5}\fs20\cf0\f0\charscalex100 {], and a direct or related}\pa
r\pard\li346\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {antiaging e}\fs20\cf
0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\charscalex100 {ects such as reduct
ion of solar elastosis [}\fs20\cf0\f0\charscalex100 {9}\fs20\cf0\f0\charscalex10
0 {]. We}\par\pard\li346\ri0\sl-200\slmult0 \fs20\cf0\f0\charscalex100 {previous
ly have described prominent in\uc1\u64257Xltrates of mast cells}\par\pard\li346\
ri0\sl-240\slmult0 \fs20\cf0\f0\charscalex100 {in the elastotic areas of melasma
skin [}\fs20\cf0\f0\charscalex100 {1}\fs20\cf0\f0\charscalex100 {] and evidence
of}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {damage to epi
dermal basal membrane, which could facilitate}\par\pard\li346\ri0\sl-226\slmult0
\fs20\cf0\f0\charscalex100 {the fall or the migration of active melanocytes and
melanin}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {into the
dermis allowing the constant hyperpigmentation in}\par\pard\li346\ri0\sl-226\sl
mult0 \fs20\cf0\f0\charscalex100 {melasma [}\fs20\cf0\f0\charscalex100 {13}\fs20
\cf0\f0\charscalex100 {]. Due to these \uc1\u64257Xndings, we wanted to prove}\p
ar\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {an intervention cap
able of inducing modi\uc1\u64257Xcations to these}\par\pard\li346\ri0\sl-226\slm
ult0 \fs20\cf0\f0\charscalex100 {atypical \uc1\u64257Xndings related in the path
ogenesis of melasma, in}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscal

ex100 {addition to modify the increased pigmentation. Therefore,}\par\pard\li346
\ri0\sl-253\slmult0 \fs20\cf0\f0\charscalex100 {we propose niacinamide as an e}\
fs20\cf0\f0\charscalex100 {\uc1\u64256X}\fs20\cf0\f0\charscalex100 {ective, inte
gral, and safe}\par\pard\li346\ri0\sl-200\slmult0 \fs20\cf0\f0\charscalex100 {th
erapeutic alternative in the melasma treatment, since it}\par\pard\li346\ri0\sl226\slmult0 \fs20\cf0\f0\charscalex100 {not only reduces pigmentation and in\uc1
\u64258Xammation, but also}\par\pard\li346\ri0\sl-226\slmult0 \fs20\cf0\f0\chars
calex100 {may reduce solar degenerative changes with minimal adverse}\par\pard\l
i346\ri0\sl-226\slmult0 \fs20\cf0\f0\charscalex100 {events.}\par\column\pard\li0
\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard
\li0\ri0\sl-213\slmult0 \fs18\cf0\par\pard\li0\ri0\sl-373\slmult0 \fs24\cf0\f0\c
harscalex100\b {References}\b0 \par\pard\li80\ri0\sl-360\slmult0 \fs18\cf0\f0\ch
arscalex100 {[1] R. Hern}\fs18\cf0\f0\charscalex100 {}\fs18\cf0\f0\charscalex100
{andez-Barrera, B. Torres-Alvarez, J. P. Castanedo-}\par\pard\li386\ri0\sl-213\s
lmult0 \fs16\cf0\f0\charscalex100 {C}\fs16\cf0\f0\charscalex100 {}\fs16\cf0\f0\ch
arscalex100 {azares, C. Oros-Ovalle, and B. Moncada, \uc1\u8220XSolar elastosis
and}\par\pard\li386\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {presence of m
ast cells as key features in the pathogenesis of}\par\pard\li386\ri0\sl-200\slmu
lt0 \fs16\cf0\f0\charscalex100 {melasma,\uc1\u8221X}{ }\fs14\cf0\f0\charscalex10
0\i {Clinical and Experimental Dermatology}\i0 \fs16\cf0\f0\charscalex100 {, vol
. 33, no.}\par\pard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {3, pp.
305\uc1\u8211X308, 2008.}\par\pard\li80\ri0\sl-213\slmult0 \fs16\cf0\f0\charscal
ex100 {[2] A. K. Gupta, M. D. Gover, K. Nouri, and S. Taylor, \uc1\u8220XThe}\pa
r\pard\li386\ri0\sl-213\slmult0 \fs16\cf0\f0\charscalex100 {treatment of melasma
: a review of clinical trials,\uc1\u8221X}{ }\fs14\cf0\f0\charscalex100\i {Journ
al of the}\i0 \par\pard\li386\ri0\sl-200\slmult0 \fs18\cf0\f0\charscalex100\i {A
merican Academy of Dermatology}\i0 \fs18\cf0\f0\charscalex100 {, vol. 55, no. 6,
pp. 1048\uc1\u8211X}\par\pard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex1
00 {1065, 2006.}\par\pard\li80\ri0\sl-226\slmult0 \fs18\cf0\f0\charscalex100 {[3
] T. Hakozaki, L. Minwalla, J. Zhuang et al., \uc1\u8220XThe e}\fs18\cf0\f0\char
scalex100 {\uc1\u64256X}\fs18\cf0\f0\charscalex100 {ect of niaci-}\par\pard\li38
6\ri0\sl-186\slmult0 \fs18\cf0\f0\charscalex100 {namide on reducing cutaneous pi
gmentation and suppression}\par\pard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\chars
calex100 {of melanosome transfer,\uc1\u8221X}{ }\fs16\cf0\f0\charscalex100\i {Br
itish Journal of Dermatology}\i0 \fs18\cf0\f0\charscalex100 {, vol.}\par\pard\li
386\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {147, no. 1, pp. 20\uc1\u8211X
31, 2002.}\par\pard\li80\ri0\sl-200\slmult0 \fs18\cf0\f0\charscalex100 {[4] H. L
. Gensler, \uc1\u8220XPrevention of photoimmunosuppression and}\par\pard\li386\r
i0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {photocarcinogenesis by topical nic
otinamide,\uc1\u8221X}{ }\fs18\cf0\f0\charscalex100\i {Nutrition and}\i0 \par\pa
rd\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100\i {Cancer}\i0 \fs18\cf0\f
0\charscalex100 {, vol. 29, no. 2, pp. 157\uc1\u8211X162, 1997.}\par\pard\li80\r
i0\sl-200\slmult0 \fs18\cf0\f0\charscalex100 {[5] A. R. Shalita, J. G. Smith, L.
C. Parish, M. S. Sofman,}\par\pard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\charsc
alex100 {and D. K. Chalker, \uc1\u8220XTopical nicotinamide compared with}\par\p
ard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {clindamycin gel in the
treatment of in\uc1\u64258Xammatory acne}\par\pard\li386\ri0\sl-213\slmult0 \fs1
8\cf0\f0\charscalex100 {vulgaris,\uc1\u8221X}{ }\fs16\cf0\f0\charscalex100\i {In
ternational Journal of Dermatology}\i0 \fs18\cf0\f0\charscalex100 {, vol. 34, no
. 6,}\par\pard\li386\ri0\sl-200\slmult0 \fs18\cf0\f0\charscalex100 {pp. 434\uc1\
u8211X437, 1995.}\par\pard\li80\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {[
6] A. Wozniacka, M. Wieczorkowska, J. Gebicki, and A. Sysa-}\par\pard\li386\ri0\
sl-213\slmult0 \fs18\cf0\f0\charscalex100 {Jedrzejowska, \uc1\u8220XTopical appl
ication of 1-methylnicotinamide}\par\pard\li386\ri0\sl-200\slmult0 \*\tx3893\fs1
6\cf0\f0\charscalex100 {in the treatment of rosacea: a pilot study,\uc1\u8221X}\
tab \fs16\cf0\f0\charscalex100\i {Clinical and}\i0 \par\pard\li386\ri0\sl-213\sl
mult0 \fs16\cf0\f0\charscalex100\i {Experimental Dermatology}\i0 \fs18\cf0\f0\ch
arscalex100 {, vol. 30, no. 6, pp. 632\uc1\u8211X635, 2005.}\par\pard\li80\ri0\s
l-213\slmult0 \fs18\cf0\f0\charscalex100 {[7] D. Levine, Z. Even-Chen, I. Lipets
et al., \uc1\u8220XPilot, multicen-}\par\pard\li386\ri0\sl-200\slmult0 \fs18\cf

0\f0\charscalex100 {ter, double-blind, randomized placebo-controlled bilateral}\
par\pard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex100 {comparative study
of a combination of calcipotriene and}\par\pard\li386\ri0\sl-213\slmult0 \*\tx38
00\fs16\cf0\f0\charscalex100 {nicotinamide for the treatment of psoriasis,\uc1\u
8221X}\tab \fs16\cf0\f0\charscalex100\i {Journal of the}\i0 \par\pard\li386\ri0\
sl-200\slmult0 \fs16\cf0\f0\charscalex100\i {American Academy of Dermatology}\i0
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atsube, and S. Inoue,}\par\pard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0\charscalex
100 {\uc1\u8220XNicotinamide increases biosynthesis of ceramides as well}\par\pa
rd\li386\ri0\sl-200\slmult0 \fs18\cf0\f0\charscalex100 {as other stratum corneum
lipids to improve the epidermal}\par\pard\li386\ri0\sl-213\slmult0 \fs18\cf0\f0
\charscalex100 {permeability barrier,\uc1\u8221X}{ }\fs16\cf0\f0\charscalex100\i
{British Journal of Dermatology}\i0 \fs18\cf0\f0\charscalex100 {, vol. 143,}\pa
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