R e v i e w A r t i c l e

Epidemiologic and genetic characteristics of alopecia areata (part 1)

Epidemiologic and genetic

characteristics of alopecia areata
(part 1)
$$$O]ROLEDQL

K E Y
WORDS
alopecia areata,
human leukocyte
antigen genes,
cytokine genes,
chemokine
genes,
polymorphism

B S T R A C T

Alopecia areata (AA) is a common, chronic, inflammatory disease resulting in an unpredictable,

non-scarring form of hair loss. It affects almost 0.1% of the general population. Although the cause
of AA is poorly understood, it is hypothesized to have an autoimmune etiology. Supporting this
theory is the fact that activated CD4 and CD8 T lymphocytes have been found in characteristic
perifollicular and intrafollicular inflammatory infiltrates of affected individuals anagen hair follicles.
AA provides an excellent opportunity to study the role of immunogenetics. In fact, various genes
that have a role in regulating immunity have also been associated with susceptibility to AA. Several
reports have indicated a significant association between AA and certain human leukocyte antigens
(HLA) genes such as HLA-DRB1*0401 and DQB1*. This review provides an overview of current
knowledge about the molecular genetics of AA. The literature review has shown overlapping gene
patterns suggestive of common pathogenic mechanisms. However, many questions remain unanswered because data about local gene expression patterns in affected tissues are still scarce.

Epidemiology
Alopecia areata (AA) is a common, chronic, in
DPPDWRU\ GLVHDVH FDXVLQJ DQ XQSUHGLFWDEOH QRQ
VFDUULQJ IRUP RI KDLU ORVV $ORSHFLD SUHVHQWV ZLWK
GLIIHUHQWFOLQLFDOSDWWHUQVVXFKDVD$ORSHFLDDUHDWD
(AA), or recurrent hair loss with patches on legs, arms,
the pubic region, scalp, lashes, or brows (1); b) Alope
cia totalis (AT), or complete (or near complete) loss of
facial and scalp hair (2); and c) Alopecia universalis
$8RUFRPSOHWHORVVRIDOOERGLO\DQGVFDOSKDLU

Acta Dermatoven APA Vol 20, 2011, No 4

$OWKRXJKJXUHVTXRWHGLQWKHOLWHUDWXUHYDU\WKH
DSSUR[LPDWHSUHYDOHQFHUDWHRI$$LVZRUOGZLGH
7KHSUHYDOHQFHUDWHPD\EHDVPXFKDVEHWZHHQ
DQGLQVRPHHWKQLFLWLHVVXFKDV.RUHDQ
,Q WKH 8QLWHG 6WDWHV DORQH  PLOOLRQ SHRSOH DS
SUR[LPDWHO\DUHDIIHFWHGZLWK$$7KHGLVHDVH
DIIHFWVERWKVH[HVDOODJHVDQGDOOHWKQLFJURXSV
$OWKRXJKWKHGLVHDVHFDQEHJLQDWDQ\WLPHRI
OLIHLWVSHDNLQFLGHQFHLVEHWZHHQDQG\HDUVRI
DJH$ERXWRISDWLHQWVSUHVHQWZLWKWKHUVWHSL

191

Epidemiologic and genetic characteristics of alopecia areata (part 1)

R e v i e w A r t i c l e

VRGHRIWKHGLVHDVHEHIRUHDJH$URXQG

RIFDVHVRFFXUEHWZHHQDJHVDQG$OWKRXJK
WKHGLVHDVHLVUHSRUWHGZLWKHTXDOIUHTXHQF\LQERWK
VH[HVPHQDUHDILFWHGZLWKVHYHUHIRUPVRIGLVHDVH
PRUHRIWHQWKDQZRPHQYV

of AA, which also increase the chances of an allergic

UHDFWLRQ
On the other hand, immunoglobulin E (IgE) is
a class of immunoglobulin essential for the allergic
response that has traditionally been associated with
DWRSLF GLVHDVH 5HFHQWO\ VRPH VWXGLHV KDYH VKRZQ
correlations between AA patients and elevation of
,J( OHYHOV  2WKHUV KDYH UHSRUWHG WKDW $$
(YLGHQFHRIWKHQRQJHQHWLFHWLRORJ\RI$$LVOLP and atopic diseases share a Th2 cytokine pattern and
LWHG6HYHUDOHQYLURQPHQWDOIDFWRUVVXFKDVLQIHFWLRQV increase levels of IgE antibodies, mast cells, and eo
VWUHVVIDFWRUVWR[LQVDQGGLHWKDYHEHHQLQFULPLQDWHG VLQRSKLOV7KLVDVVRFLDWLRQPD\EHFDXVHGE\
EXWQRQHFRQUPHG$VWXG\KDVGHWHFWHGF\WR a shift from a Th1 response in early AA to a more
PHJDORYLUXV &09 '1$ LQ $$ VFDOS OHVLRQV  FKURQLF 7K LPPXQH SUROH ZLWK VHFRQGDU\ %FHOO
EXW WKHVH QGLQJV UHPDLQHG XQFRQUPHG LQ DQRWK VWLPXODWLRQDQGSRVVLEOH,J(FODVVVZLWFKLQJ
HU VWXG\ LQ ZKLFK 3&5 DQDO\VLV RI SHULSKHUDO EORRG
mononuclear cells of patients showed no relation be
WZHHQ $$ DQG ODWHQW RU DFWLYH &09 LQIHFWLRQ 
7KHJHQHWLFIDFWRUVIRU$$DUHLPSRUWDQW7KHUH
Similarly, the association of Helicobacter pylori with AA
LVDKLJKIUHTXHQF\RIDSRVLWLYHIDPLO\KLVWRU\LQ$$
UHPDLQVLQFRQFOXVLYH
5HFHQW VWXGLHV LQ KXPDQV KDYH OHG WR PXFK HYL SDWLHQWVYDU\LQJIURPWRDQGDOLIHWLPHULVN
GHQFHLQVXSSRUWRIDQDXWRLPPXQHHWLRORJ\7KHSUR RI*HQHWLFLQXHQFHLVDOVRVXJJHVWHGE\
FHVVDSSHDUVWREH7FHOOPHGLDWHG$QWLERGLHVDJDLQVW the occurrence of AA in twins, with a concordance
anagen stage hair follicle structures have been detect RILQPRQR]\JRWLFWZLQV6LPLODUO\DKLJKHU
HGLQDIIHFWHGSDWLHQWVDQGLQPRXVHPRGHOV LQFLGHQFH RI $$  LV VHHQ LQ LQGLYLGXDOV ZLWK
8VLQJ LPPXQRXRUHVFHQFH DQWLERGLHV WR DQDJHQ Down syndrome compared to the general population
SKDVHKDLUIROOLFOHVZHUHIRXQGLQDVPDQ\DVRI $ORSHFLDDUHDWDLVFRQVLGHUHGDSRO\JHQLFGLVHDVH
SDWLHQWV ZLWK $$ FRPSDUHG WR IHZHU WKDQ  RI that depends on the additive action of several major
FRQWURO VXEMHFWV  +LVWRORJLFDO QGLQJ RI D GHQVH VXVFHSWLELOLW\JHQHV,QWKHODVWGHFDGHWKHSDUDGLJP
SHULIROOLFXODU DQG LQWUDIROOLFXODU LQOWUDWH RI SULPDU RIDFRPSOH[WUDLWRUPXOWLIDFWRULDOWUDLWKDVEH
ily CD4+ and CD8+ lymphocytes is closely associated come acceptable because genetic and ecological fac
ZLWK G\VWURSKLF DQDJHQ VWDJH KDLU IROOLFOHV  7KH WRUVVHHPWRFRQWULEXWHLQWKHQDOSKHQRW\SHRI$$
transmission of AA by T lymphocytes cultivated from 7KHWHUPFRPSOH[WUDLWLVXVHGWR
affected scalp cells and transferred to human scalp GHVFULEHSKHQRW\SHVWKDWGRQRWH[KLELWFODVVLF0HQ
H[SODQWV RQ D VHYHUH FRPELQHG LPPXQRGHFLHQF\ delian inheritance attributable to a single gene locus
but do have a genetic component, as demonstrated
PRXVHPRGHOKDVEHHQGHPRQVWUDWHG
E\ WZLQ DGRSWLRQ DQG HSLGHPLRORJLFDO VWXGLHV 
There are four separate observations in favor of poly
JHQLFLQKHULWDQFHLWKHKLJKSUHYDOHQFHRIWKH
$WRSLFGLVHDVHVKDYHEHHQDVVRFLDWHGZLWKWR WUDLW W\SLFDO RI FRPSOH[ WUDLWV IRU ZKLFK WKH SUHGLV
RI$$SDWLHQWV7KHUHIRUHVHYHUDOVWXG posing alleles are more common than the relatively
ies have suggested that a history of atopic diseases UDUHPXWDWLRQVLGHQWLHGIRU0HQGHOLDQGLVRUGHUVLL
such as asthma, atopic dermatitis, and hay fever are WKH*DXVVLDQFXUYHRIGLVWULEXWLRQIRUERWKWKHVWDJHV
ULVNIDFWRUVIRU$$0RUHRYHUPXWDWLRQVLQ of disease progression and the distribution of the dis
FHUWDLQJHQHVOLNHWKHODJJULQJHQH)/*KDYHEHHQ ease, with a threshold effect that may be lowered, for
suggested as a strong risk factor for atopic dermati H[DPSOHE\WKHSUHVHQFHRIDSDUWLFXODU+/$KDSOR
WLV  +HQFH VRPH LQYHVWLJDWRUV K\SRWKHVL]H type or autoimmune susceptibility (51); (iii) heritabil
that mutations in these types of genes may also play LW\DVGHQHGE\ERWKWKHIUHTXHQF\RIDIIHFWHGIDPLO\
a role in AA, particularly in the severe form of AA members, ranging from 3% to 42% (44), and concor
ZLWKFRPRUELGDWRSLFGLVHDVH0RUHRYHUWKH dance in twins (52); and (iv) the presence of congenital
IDFWWKDWWKHSURJQRVLVIRUKDLUUHJURZWKLVZRUVHLQ AA, strongly suggesting the contribution of genetic
DWRSLFSDWLHQWVWKDQLQQRQDWRSLFRQHVPD\EHDGGL IDFWRUV6XQGEHUJHWDOKDYHUHSRUWHGWKH
tional evidence that atopic diseases are associated with LGHQWLFDWLRQ RI SRWHQWLDO VXVFHSWLELOLW\ ORFL IRU $$
LQFUHDVHGULVNRI$$7KHUHDVRQIRUWKLVDSSDU SKHQRW\SHLQDQH[SHULPHQWDOPRXVHPRGHO,QDQDW
HQWKLJKHUIUHTXHQF\RIDWRS\LQ$$PD\EHDVFULEHG tempt to determine the genetic basis of AA, a number
WRWKHJHQHVLQYROYHGLQWKHLQDPPDWRU\FRPSRQHQW of association studies for suspected genes have been

Immunogenic factors

Genetic factors

Alopecia areata and atopy

192

Acta Dermatoven APA Vol 20, 2011, No 4

R e v i e w A r t i c l e

Epidemiologic and genetic characteristics of alopecia areata (part 1)

SHUIRUPHG6HYHUDORIWKHVHVWXGLHVKDYHVXJJHVWHGD
7KHDVVRFLDWLRQRI$$ZLWK+/$'5DQG+/$
VLJQLFDQW DVVRFLDWLRQ RI $$ ZLWK QXPHURXV FDQGL '4 VXSSRUWV WKH QRWLRQ WKDW &' 7 FHOOV DUH LQ
GDWHJHQHV
YROYHGLQWKHGLVHDVHSURFHVV+/$'5DQG'4PRO
ecules are responsible for presenting antigen to CD4+
7 FHOOV  ,Q DGGLWLRQ WLVVXH KLVWRORJ\ RI DIIHFWHG
areas in AA demonstrates the presence of a perifol
*HQHWLFDQGSURWHRPLFVWHFKQRORJLHVIRUDXWRLP OLFXODU&'O\PSKRF\WLFLQOWUDWHDVZHOODVD&'
mune diseases have developed rapidly in the last de LQWUDIROOLFXODULQOWUDWH
FDGH 7KHVH WHFKQRORJLHV KDYH OHG WR WKH LGHQWLFD
(DUO\VWXGLHVRQ+/$&ODVV,IDLOHGWRVKRZDFRQ
tion of many candidate genes in humans that confer VLVWHQWOLQNDJHZLWKDVLQJOHDQWLJHQDOWKRXJK+/$
susceptibility to the development of autoimmunity in $%$ZDQG%DOOHOHVKDYHHDFKEHHQUHSRUW
FDVHVRI$$7KHUHDUHWZRPDLQDSSURDFKHVWRGH ed as being associated with a high prevalence of AA
WHUPLQLQJWKHJHQHWLFFRQWULEXWLRQVWRDGLVHDVH7KH LQWZRIDPLOLHV$VVRFLDWLRQVEHWZHHQ+/$%
UVW LV WR FRQGXFW DVVRFLDWLRQ VWXGLHV LQ ZKLFK DQ LQ)LQQLVKSDWLHQWV+/$%LQ,VUDHOLVDQG%DQG
LQGLYLGXDOFDQGLGDWHJHQHLVH[DPLQHGIRUDVVRFLDWLRQ % LQ 5XVVLDQV KDYH DOVR EHHQ VXJJHVWHG 
ZLWKWKHFRQGLWLRQ7KHGLVDGYDQWDJHRIWKLVDSSURDFK .DOLVKHWDOKDYHVXJJHVWHGWKDWQRUPDOKDLUHSLWKH
is the possibility of false associations as a result of OLXP LV DQ LPPXQHSULYLOHJHG VLWH GXH WR LWV ODFN RI
OLQNDJH GLVHTXLOLEULXP 7KHUHIRUH LW LV QHFHVVDU\ WR +/$$ % DQG & H[SUHVVLRQ  7 FHOO UHFRJQL
FRQGXFWIUHTXHQF\VWXGLHVLQPXOWLSOHSRSXODWLRQV tion of follicular autoantigens may be induced by the
7KH VHFRQG DSSURDFK LV WR SHUIRUP JHQRPHZLGH LQFUHDVHGH[SUHVVLRQRI+/$$%DQG&DVZHOODV
VHDUFKHVZKLFKKDYHUHFHQWO\VWDUWHGEHLQJXWLOL]HG +/$'5 GXULQJ LQDPPDWRU\ FRQGLWLRQV UHVXOWLQJ
IRULGHQWLFDWLRQRIFKURPRVRPDOUHJLRQVDVVRFLDWHG LQDORVVRILPPXQHSULYLOHJH
ZLWKGLVHDVHULVN7KLVJHQRPHZLGHDSSURDFKKDVWKH
0RUHFRQVLVWHQWDVVRFLDWLRQVKDYHEHHQIRXQGEH
advantage that it is not biased by an initial hypoth WZHHQ$$DQG&ODVV,,KDSORW\SHV5HFXUUHQWGLUHFW
HVLV+RZHYHUGHWHUPLQDWLRQRIFKURPRVRPDOUHJLRQV OLQNDJHDQDO\VLVDGYRFDWHVIRUDOLQNEHWZHHQWKH+/$
ZLWK JHQRPHZLGH VFUHHQV LV RQO\ WKH UVW VWHS DQG class II region and AA, showing an LOD (logarithm
PXFKDGGLWLRQDOZRUNLVUHTXLUHGWRPDSWKHULVNWR RIRGGVVFRUHRIIRU+/$'4%DWUHFRPEL
VSHFLF JHQHV 7KH IROORZLQJ FDQGLGDWH JHQHV KDYH QDWLRQ5HFHQWO\DUHSRUWIURPWKH8QLWHG6WDWHV
EHHQVWXGLHG
VWDWHGWKDW+/$'4%   DOOHOHVZHUH
SUHVHQWLQRIDOO$$FDVHVUHJDUGOHVVRISKHQR
W\SHDQGWKLVSUHVHQFHLQFUHDVHGWRLQFDVHVZLWK
$7RU$8RGGVUDWLR p 
$OVR '4%  '4 E\ VHURORJ\ ZDV IRXQG WR
EHVLJQLFDQWO\H[SUHVVHGRQO\LQDVVRFLDWLRQZLWK$$
7KH PDMRU KLVWRFRPSDWLELOLW\ FRPSOH[ 0+& WRWDOLVDQGXQLYHUVDOLV2WKHUVWXGLHVLP
region represents the major susceptibility locus on SOLFDWHRWKHU'4%DOOHOHVLQ$$VXFKDV'4% 
FKURPRVRPH  ZLWKLQ WKH ORFXV S 0RVW RI LWV '4% DQG'4% 7XUNLVKSDWLHQWVKDG
JHQHVHQFRGHFHOOVXUIDFHDQWLJHQSUHVHQWLQJSURWHLQV D KLJKHU IUHTXHQF\ RI +/$'4 +/$'4 
7KHVHDUHGLYLGHGLQWRWKUHHFODVVHV+XPDQOHXNRF\WH DQG '4%   ,Q WKH 'DQLVK SRSXODWLRQ VXE
DQWLJHQFODVV,+/$,VXEFODVVLHGDV$%DQG& MHFWVZLWK'4$ '4% DQG'3$ 
DUHH[SUHVVHGRQWKHVXUIDFHRIDOOQXFOHDWHGFHOOVDQG DOOHOHV FDUULHG D JUHDWHU ULVN RI GHYHORSLQJ $$ 
SUHVHQW SHSWLGHV WR &' 7 FHOOV 7KH &' O\P $QDO\VLV RI WKH FRPELQHG SUHVHQFH RI '4% 
phocytes have the capacity to recognize cellular anti DQG'3$ LQ$$VXJJHVWVWKDWDQDGGLWLYHULVN
gens presented in association with class I via their T HIIHFW V\QHUJLVP RU LQWHUDFWLRQ H[LVWV EHWZHHQ WKH
FHOOUHFHSWRUV,QFRQWUDVWFODVV,,DQWLJHQV'3'0 '4%  DQG '3$  DOOHOHV ZKLFK DUH VLWX
'2$'2%'4DQG'5DUHQRUPDOO\H[SUHVVHGRQ DWHGDWGLIIHUHQW+/$FODVV,,ORFL0RUHUHFHQWO\
DQWLJHQSUHVHQWLQJFHOOV$3&VVXFKDVPDFURSKDJHV +DQ&KLQHVHLQGLYLGXDOVZLWK$$ZHUHIRXQGWRKDYHD
DQG/DQJHUKDQVFHOOVDQGH[SUHVVLRQPD\EHLQGXFHG KLJKHUIUHTXHQF\RI+/$'4$ '4% 
RQRWKHUQXFOHDWHGFHOOVGXULQJLQDPPDWRU\SURFHVV DQG'4$ 
HVVXFKDV$$&'O\PSKRF\WHVPD\UHF
0DQ\JHQHWLFDQDO\VLVVWXGLHVLQ$$KDYHSULPDU
RJQL]HDQWLJHQSOXVFODVV,,FRPSOH[HVRQ$3&V LO\IRFXVHGRQWKH+/$'JHQHV0+&FODVV,,HQ
7KH UHPDLQGHU FRPSULVHV WKH +/$ FODVV ,,, UHJLRQ coding) as the most likely region for genes that regu
that encodes components of the complement system, late susceptibility, severity of, or resistance to disease
such as complement factors, tumor necrosis factor 7KHPDMRULW\RIWKHVHVWXGLHVKDYHLQGLFDWHGDQ
71)DQGKHDWVKRFNSURWHLQ+6S
LQFUHDVHG IUHTXHQF\ RI '5 '5 '5 DQG '5

Candidate genes

Histocompatibility locus antigen

(HLA) genes

Acta Dermatoven APA Vol 20, 2011, No 4

193

Epidemiologic and genetic characteristics of alopecia areata (part 1)

(DUOLHUVWXGLHVXVLQJVHURORJLFDOW\SLQJWHFK
QLTXHVVXJJHVWHGWKDW'5DQG'5ZHUHDVVRFLDWHG
ZLWKVHYHUHIRUPVRI$$+/$'5% LV
DVVRFLDWHGZLWKSDWFK\$$ZKHUHDV'5
'5'5'5DQG+/$'5% 
DUHVLJQLFDQWO\LQFUHDVHGLQORQJVWDQGLQJ$7$8SD
WLHQWV$7XUNLVKVWXG\KRZHYHUGLGQRWUHYHDO
DVVRFLDWLRQVZLWK'5DQG'5'5LQ$$
Another study has demonstrated a predisposing effect
RI'5% '5% ZDVPRVWSUHYDOHQWLQWKH
(XURSHDQSRSXODWLRQ
&HUWDLQ +/$ DVVRFLDWLRQV RQ WKH RWKHU KDQG
may provide relative protection from AA, as has been
SURSRVHGIRU+/$'5ZDDQG+/$'5% 
7KHIUHTXHQFLHVRI+/$'5DDQG'5
KDYHEHHQUHSRUWHGWREHORZHULQ$$FDVHV6LPL
ODUO\DGHFUHDVHLQ'5ZDVREVHUYHGDPRQJPDOH$$
SDWLHQWVSRVVLEO\VXJJHVWLQJDSURWHFWLYHUROHRI
'5$QRWKHUVWXG\RID%HOJLDQ*HUPDQSRSXODWLRQ
IRXQGWKDW'5% PRVWVXJJHVWLYHRI'5% 
was a protective factor against AA compared to con
WUROV+RZHYHUWKHUHVXOWVDOVRLQGLFDWHGWKDWWKH
SURWHFWLYH HIIHFW ZDV IUHTXHQWO\ SUHVHQW LQ LQGLYLGX
als with a familial history of AA and less commonly
DPRQJVSRUDGLFFDVHV

R e v i e w A r t i c l e

,QDGGLWLRQWKHUHDUHVHYHUDORWKHUQRQ+/$JHQHV
WKDWPDSZLWKLQWKH0+&UHJLRQWKDWPD\EHSULPDU\
RU DGGLWLRQDO VXVFHSWLELOLW\ ORFL DVVRFLDWHG ZLWK $$
2QHSRVVLEOHFDQGLGDWHJHQHIRU$$VXVFHSWLELOLW\LV
Notch4, which maps to the centromeric end of the
+/$FODVV,,,UHJLRQNEWHORPHULFWR'5%
In mammals, Notch 14 genes are known to be in
YROYHGLQDQJLRJHQHVLVKDLUJURZWKDQG7FHOOPDWX
UDWLRQ7KHKXPDQ1RWFKJHQHLVORFDWHGRQ
FKURPRVRPHS,QDFDVHFRQWUROVWXG\VHYHUDO
associations have been reported between Notch4 gene
polymorphisms and mild to severe AA, particularly
ZLWK SRO\PRUSKLVPV DW SRVLWLRQV  DQG 
7KHLQLWLDODQDO\VHVKDYHVKRZQDVLJQLFDQWDVVRFLD
tion of AA in the overall data set with the Notch4
7& SRO\PRUSKLVP  p   EXW QRW ZLWK
1RWFK$*SRO\PRUSKLVP

Conclusion
To conclude, we have provided an overview of
available current knowledge about the molecular
JHQHWLFV RI $$ 9DULRXV +/$ JHQHV VXFK DV +/$
'5% DQG'4% WKDWKDYHDUROHLQUHJX
lating immunity have been associated with suscepti
ELOLW\WR$$

Table 1. Various HLA genes have been associated with susceptibility to alopecia alopecia areata among
several populations. AA - alopecia areata, AU - alopecia universalis, AT - alopecia totalis, USA United States of America, UK - United Kingdom of Great Britain.
Alopecia HLA class I

Population HLA class II

AA

Turkish
5XVVLDQV
Israelis
Chinese
5XVVLDQV
Americans
)LQQV
Turkish

A1
%
%
%&Z 
%
%
%%
%&:

AU/AT

Population

'4'4% 
'4'4% 
'5
'5
'5
'5
'5'5
'3:

US
Denmark
US
Italy
8.
Denmark
US
Denmark

'4'4% 
'5'5% 
'4'45 

US
US
US

R EFERENCES

194

1.

6FKZDUW]5$-DQQLJHU&.$ORSHFLDDUHDWD&XWLV



6LPSVRQ1%$ORSHFLDDUHDWD,Q5RRN$'DZEHU5HGLWRUV'LVHDVHVRIWKHKDLUDQGVFDOS/RQGRQ
%ODFNZHOO6FLHQWLF3XEOLFDWLRQVS

3.

7D]L$KQLQL5GL*LRYLQH)60F'RQDJK$-0HVVHQJHU$*$PDGRX&&R[$'XII*:&RUN0-
6WUXFWXUHDQGSRO\PRUSKLVPRIWKHKXPDQJHQHIRUWKHLQWHUIHURQLQGXFHGSSURWHLQ0;HYLGHQFHRI
DVVRFLDWLRQZLWKDORSHFLDDUHDWDLQWKH'RZQV\QGURPHUHJLRQ+XP*HQHW
Acta Dermatoven APA Vol 20, 2011, No 4

R e v i e w A r t i c l e

Epidemiologic and genetic characteristics of alopecia areata (part 1)

4.

7DN :- &KXQJ <6 5R %, $ FOLQLFDO VWXG\ RQ DORSHFLD DUHDWD  .RUHDQ - 'HUPDWRO


5.

6DIDYL.+0XOOHU6$6XPDQ9-HWDO,QFLGHQFHRIDORSHFLDDUHDWDLQ2OPVWHG&RXQW\0LQQHVRWD
WKURXJK0D\R&OLQ3URF

6.

3ULFH9+$ORSHFLDDUHDWDFOLQLFDODVSHFWV-,QYHVW'HUPDWRO6



6DZD\D 0( +RUGLQVN\ 0. $GYDQFHV LQ DORSHFLD DUHDWD DQG DQGURJHQHWLF DORSHFLD $GY 'HUPDWRO


8.

0DGDQL66KDSLUR-$ORSHFLDDUHDWDXSGDWH-$P$FDG'HUPDWRO



'DZEHU535GH%HUNHU':RMQDURZVND)'LVRUGHUVRIKDLU,Q&KDPSLRQ5+%XUWRQ-/%XUQV'$
%UHDWKQDFK60HGLWRUV7H[WERRNRIGHUPDWRORJ\2[IRUG%ODFNZHOO6FLHQFHS

 0RUHQR*$)HUUDQGR-$ORSHFLDDUHDWD0HG&XWDQ,EHUR/DWLQD$PHULFDQD
11. 3ULFH 9+ &RORPEH %: +HULWDEOH IDFWRUV GLVWLQJXLVK WZR W\SHV RI DORSHFLD DUHDWD 'HUPDWRO &OLQ

 &DPDFKR)$ORSHFLDDUHDWDFOLQLFDOIHDWXUHV'HUPDWRSDWKRORJ\,Q&DPDFKR)0RQWDJQD:HGLWRUV
7ULFKRORJ\GLVHDVHVRIWKHSLORVHEDFHXVIROOLFOH0DGULG$XOD0HGLFD*URXSS
13. 'XGGD6XEUDPDQ\D5$OH[LV$)6LX.6LQKD$$$ORSHFLDDUHDWDJHQHWLFFRPSOH[LW\XQGHUOLHVFOLQLFDO
KHWHURJHQHLW\(XU-'HUPDWRO
14. 7RVWL$/D3ODFD03ODFXFFL)HWDO1RFRUUHODWLRQEHWZHHQF\WRPHJDORYLUXVDQGDORSHFLDDUHDWD-,QYHVW
'HUPDWRO
15. .DOLVK56*LOKDU$$ORSHFLDDUHDWDDXWRLPPXQLW\WKHHYLGHQFHLVFRPSHOOLQJ-,QYHVW'HUPDWRO6\PS
3URF
16. 0F(OZHH.-%RJJHVV'2OLYU\72OLYHU5):KLWLQJ'7RELQ'-%\VWU\Q-&.LQJ/(-U6XQGEHUJ-3
&RPSDULVRQRIDORSHFLDDUHDWDLQKXPDQDQGQRQKXPDQPDPPDOLDQVSHFLHV3DWKRELRORJ\
 7RELQ'-6XQGEHUJ-3.LQJ/(-U%RJJHVV'%\VWU\Q-&$XWRDQWLERGLHVWRKDLUIROOLFOHVLQ&++H-
PLFHZLWKDORSHFLDDUHDWDOLNHKDLUORVV-,QYHVW'HUPDWRO
18. 0HG6FDSH5HIHUHQFH>,QWHUQHW@1HZ<RUN:HE0'//&F%ROGXF&/XL+HWDO$ORSHFLD
$UHDWD6HS>FLWHG'HF@$YDLODEOHIURPKWWSHPHGLFLQHPHGVFDSHFRPDUWLFOH
RYHUYLHZ
 *LOKDU$8OOPDQQ<%HUNXW]NL7$VV\%.DOLVK56$XWRLPPXQHKDLUORVVDORSHFLDDUHDWDWUDQVIHUUHG
E\7O\PSKRF\WHVWRKXPDQVFDOSH[SODQWVRQ6&,'PLFH-&OLQ,QYHVW
 ,NHGD7$QHZFODVVLFDWLRQRIDORSHFLDDUHDWD'HUPDWRORJLFD
 7DQ(7D\<.*RK&/&KLQ*LDP<7KHSDWWHUQDQGSUROHRIDORSHFLDDUHDWDLQ6LQJDSRUHDVWXG\RI
$VLDQV,QW-'HUPDWRO
 *RK&)LQNHO0&KULVWRV3-6LQKD$$3UROHRISDWLHQWVZLWKDORSHFLDDUHDWDDVVRFLDWLRQVRIGLVHDVH
VXEW\SHV ZLWK DWRS\ DXWRLPPXQH GLVHDVH DQG SRVLWLYH IDPLO\ KLVWRU\ - (XU $FDG 'HUPDWRO 9HQHUHRO

 ;LDR)/<DQJ6/LX-%+H33<DQJ-&XL<HWDO7KHHSLGHPLRORJ\RIFKLOGKRRGDORSHFLDDUHDWDLQ
&KLQDDVWXG\RISDWLHQWV3HGLDWU'HUPDWRO
 1DQGD$$O)RUX]DQ$6$O+DVDZL)$ORSHFLDDUHDWDLQFKLOGUHQDFOLQLFDOSUROH3HGLDWU'HUPDWRO

 %DUDKPDQL16FKDEDWK0%'XYLF0+LVWRU\RIDWRS\RUDXWRLPPXQLW\LQFUHDVHVULVNRIDORSHFLDDUHDWD
-$P$FDG'HUPDWRO
 3DOPHU&1,UYLQH$'7HUURQ.ZLDWNRZVNL$=KDR</LDR+/HH63HWDO&RPPRQORVVRIIXQFWLRQ
YDULDQWVRIWKHHSLGHUPDOEDUULHUSURWHLQODJJULQDUHDPDMRUSUHGLVSRVLQJIDFWRUIRUDWRSLFGHUPDWLWLV1DW
*HQHW
Acta Dermatoven APA Vol 20, 2011, No 4

195

Epidemiologic and genetic characteristics of alopecia areata (part 1)

R e v i e w A r t i c l e

 5XHWKHU$6WROO06FKZDU]76FKUHLEHU6)ROVWHU+ROVW5)LODJJULQORVVRIIXQFWLRQYDULDQWFRQWULEXWHV
WRDWRSLFGHUPDWLWLVULVNLQWKHSRSXODWLRQRIQRUWKHUQ*HUPDQ\%U-'HUPDWRO
 6WHPPOHU63DUZH]43HWUDVFK3DUZH]((SSOHQ-7+RIIMDQ67ZRFRPPRQORVVRIIXQFWLRQPXWDWLRQV
ZLWKLQWKHODJJULQJHQHSUHGLVSRVHIRUHDUO\RQVHWRIDWRSLFGHUPDWLWLV-,QYHVW'HUPDWRO
 :HLGLQJHU 6 ,OOLJ 7 %DXUHFKW + ,UYLQH $' 5RGULJXH] ( 'LD]/DFDYD $ HW DO /RVVRIIXQFWLRQ
YDULDWLRQVZLWKLQWKHODJJULQJHQHSUHGLVSRVHIRUDWRSLFGHUPDWLWLVZLWKDOOHUJLFVHQVLWL]DWLRQV-$OOHUJ\
&OLQ,PPXQRO
 :HLGLQJHU65RGULJXH](6WDKO&:DJHQSIHLO6.ORSS1,OOLJ7HWDO)LODJJULQPXWDWLRQVVWURQJO\
SUHGLVSRVHWRHDUO\RQVHWDQGH[WULQVLFDWRSLFGHUPDWLWLV-,QYHVW'HUPDWRO
31. %DUNHU -1 3DOPHU &1 =KDR < /LDR + +XOO 35 /HH 63 HW DO 1XOO PXWDWLRQV LQ WKH ODJJULQ JHQH
)/*GHWHUPLQHPDMRUVXVFHSWLELOLW\WRHDUO\RQVHWDWRSLFGHUPDWLWLVWKDWSHUVLVWVLQWRDGXOWKRRG-,QYHVW
'HUPDWRO
 0RUDU 1 &RRNVRQ :2 +DUSHU -, 0RIIDWW 0) )LODJJULQ PXWDWLRQV LQ FKLOGUHQ ZLWK VHYHUH DWRSLF
GHUPDWLWLV-,QYHVW'HUPDWRO-XO
33. %HW]5&3IRUU-)ODTXHU$5HGOHU6+DQQHNHQ6(LJHOVKRYHQ6.RUWP$.7WLQJ7/DPEHUW-'H
:HHUW-+LOOPHU$06FKPDHO&:LHQNHU7).UXVH5/XW]*%ODXPHLVHU%1|WKHQ00/RVVRI
IXQFWLRQPXWDWLRQVLQWKHODJJULQJHQHDQGDORSHFLDDUHDWDVWURQJULVNIDFWRUIRUDVHYHUHFRXUVHRIGLVHDVH
LQSDWLHQWVFRPRUELGIRUDWRSLFGLVHDVH-,QYHVW'HUPDWRO1RY
34. 5LQJ-3U]\ELOOD%5X]LFND7+DQGERRNRIDWRSLFHF]HPD%HUOLQ6SULQJHUS
35. 7RNXUD < 6XJLWD . .DEDVKLPD . ,WR 7 <DJL + $ORSHFLD XQLYHUVDOLV DVVRFLDWHG ZLWK LPSDLUHG
LQWHUOHXNLQSURGXFWLRQDQGORZVHUXP,J(OHYHO-$P$FDG'HUPDWRO6
36. .DVXPDJLF+DOLORYLF(3URKLF$6HUXPOHYHOVRIWRWDOLPPXQRJOREXOLQHLQSDWLHQWVZLWKDORSHFLDDUHDWD
UHODWLRQVKLSZLWKFOLQLFDOW\SHRIWKHGLVHDVH$FWD'HUPDWRYHQHURO&URDW
 5RVHOLQR$0$OPHLGD$0+LSSROLWR0$&HUTXHLUD%&0DIIHL&00HQH]HV-%9LHLUD5($VVLV6/
$OL6$&OLQLFDOHSLGHPLRORJLFVWXG\RIDORSHFLDDUHDWD,QW-'HUPDWRO
38. %RULVK / 5RVHQZDVVHU /- &\WRNLQHV LQ DOOHUJLF LQDPPDWLRQ ,Q $GNLQVRQ 1) -U <XQJLQJHU -:
%XVVH::%RFKQHU%6+ROJDWH676LPRQV)(5HGLWRUV0LGGOHWRQVDOOHUJ\SULQFLSOHVDQGSUDFWLFH
3KLODGHOSKLD0RVE\S
 3U]\ELOOD%5LQJ-9RON07RWDO,J(OHYHOVLQWKHVHUXPLQGHUPDWRORJLFGLVHDVHV+DXWDU]W

 (OVWRQ'00F&ROORXJK0/%HUJIHOG:)/LUDQ]R02+HLEHO0(RVLQRSKLOVLQEURXVWUDFWVDQGQHDU
KDLUEXOEVDKHOSIXOGLDJQRVWLFIHDWXUHRIDORSHFLDDUHDWD-$P$FDG'HUPDWRO
41. (O 'DURXWL 0 0DU]RXN 6$ 6KDUDZL ( (RVLQRSKLOV LQ EURXV WUDFWV DQG QHDU KDLU EXOEV D KHOSIXO
GLDJQRVWLFIHDWXUHRIDORSHFLDDUHDWD-$P$FDG'HUPDWRO
 )DNNDU10=$WWLD($60RXVVD06(YDOXDWLRQRIWRWDOVHUXPLPPXQRJOREXOLQ(LQDORSHFLDDUHDWD(J\
'HUP-
43. *LOKDU$.DOLVK56$ORSHFLDDUHDWDDWLVVXHVSHFLFDXWRLPPXQHGLVHDVHRIWKHKDLUIROOLFOH$XWRLPPXQ
5HY
44. *UHHQ-6LQFODLU5'*HQHWLFVRIDORSHFLDDUHDWD$XVWUDODV-'HUPDWRO
45. 0F'RQDJK $- 7D]L$KQLQL 5 (SLGHPLRORJ\ DQG JHQHWLFV RI DORSHFLD DUHDWD &OLQ ([S 'HUPDWRO

46. 6FHUUL/3DFH-/,GHQWLFDOWZLQVZLWKLGHQWLFDODORSHFLDDUHDWD-$P$FDG'HUPDWRO
 0F(OZHH.-)UH\VFKPLGW3DXO3=LHJOHU$+DSSOH5+RIIPDQQ5*HQHWLFVXVFHSWLELOLW\DQGVHYHULW\RI
DORSHFLDDUHDWDLQKXPDQDQGDQLPDOPRGHOV(XU-'HUPDWRO
48. 0F(OZHH.-+RIIPDQQ5$ORSHFLDDUHDWDDQLPDOPRGHOV&OLQ([S'HUPDWRO

196

Acta Dermatoven APA Vol 20, 2011, No 4

R e v i e w A r t i c l e

Epidemiologic and genetic characteristics of alopecia areata (part 1)

 /DQGHU(66FKRUN1-*HQHWLFGLVVHFWLRQRIFRPSOH[WUDLWV6FLHQFH
 $LWD90&KULVWLDQR$07KHJHQHWLFVRIDORSHFLDDUHDWD'HUPDWRO7KHU
51. :HOVK($&ODUN++(SVWHLQ-'5HYHLOOH6='XYLF0+XPDQOHXNRF\WHDQWLJHQ'4% DOOHOHVDUH
DVVRFLDWHGZLWKDORSHFLDDUHDWD-,QYHVW'HUPDWRO
 -DFNRZ&3XIIHU1+RUGLQVN\01HOVRQ-7DUUDQG-'XYLF0$ORSHFLDDUHDWDDQGF\WRPHJDORYLUXV
LQIHFWLRQLQWZLQVJHQHVYHUVXVHQYLURQPHQW"-$P$FDG'HUPDWRO
53. GH9LUDJK3$*LDQDGGD%/HY\0/&RQJHQLWDODORSHFLDDUHDWD'HUPDWRORJ\
54. %DUGD]]L ) 1HUL , 5DRQH % 3DWUL]L $ &RQJHQLWDO DORSHFLD DUHDWD $QRWKHU FDVH 'HUPDWRORJ\

55. %HUHNHW$7XUDQ6$OSHU*&RPX6$OSD\+$NDOLQ)7ZRSDWLHQWVZLWK.DEXNLV\QGURPHSUHVHQWLQJZLWK
HQGRFULQHSUREOHPV-3HGLDWU(QGRFULQRO0HWDE
56. &URZGHU-$)ULHGHQ,-3ULFH9+$ORSHFLDDUHDWDLQLQIDQWVDQGQHZERUQV3HGLDWU'HUPDWRO
8.
 6XQGEHUJ -3 2OLYHU 5) 0F(OZHH .- .LQJ /( -U $ORSHFLD DUHDWD LQ KXPDQV DQG RWKHU PDPPDOLDQ
VSHFLHV-,QYHVW'HUPDWRO66
58. 0HVVHQJHU$*%OHHKHQ66([SUHVVLRQRI+/$'5E\DQDJHQKDLUIROOLFOHVLQDORSHFLDDUHDWD-,QYHVW
'HUPDWRO
 %U|FNHU(%(FKWHUQDFKW+DSSOH.+DPP++DSSOH5$EQRUPDOH[SUHVVLRQRIFODVV,DQGFODVV,,PDMRU
KLVWRFRPSDWLELOLW\DQWLJHQVLQDORSHFLDDUHDWDPRGXODWLRQE\WRSLFDOLPPXQRWKHUDS\-,QYHVW'HUPDWRO

 5RELQVRQ-:DOOHU0-3DUKDP3GH*URRW1%RQWURS5.HQQHG\/-6WRHKU30DUVK6*,0*7+/$
DQG,0*70+&VHTXHQFHGDWDEDVHVIRUWKHVWXG\RIWKHPDMRUKLVWRFRPSDWLELOLW\FRPSOH[1XFOHLF$FLGV
5HV
61. 7RGHV7D\ORU17XUQHU5:RRG*66WUDWWH370RUKHQQ9%7FHOOVXESRSXODWLRQVLQDORSHFLDDUHDWD-
$P$FDG'HUPDWRO3W
 0FGRQDJK$-*0HVVHQJHU$*$ORSHFLDDUHDWD&OLQLFVLQ'HUPDWRORJ\
63. .LDQWR85HXQDOD7.DUYRQHQ-/DVVXV$7LLOLNDLQHQ$+/$%LQDORSHFLDDUHDWD$UFK'HUPDWRO

64. +DFKDP=DGHK6%UDXWEDU&&RKHQ&&RKHQ7+/$DQGDORSHFLDDUHDWDLQ-HUXVDOHP7LVVXH$QWLJHQV

65. $YHUEDNK (9 3RVSHORY /( +/$ DQWLJHQV LQ SDWLHQWV ZLWK DORSHFLD DUHDWD 9HVWQ 'HUPDWRO 9HQHURO

66. &DUWHU'0-HJDVRWK\%9$ORSHFLDDUHDWDDQG'RZQV\QGURPH$UFK'HUPDWRO
 &RORPEH%:/RX&'3ULFH9+7KHJHQHWLFEDVLVRIDORSHFLDDUHDWD+/$DVVRFLDWLRQVZLWKSDWFK\
DORSHFLDDUHDWDYHUVXVDORSHFLDWRWDOLVDQGDORSHFLDXQLYHUVDOLV-,QYHVW'HUPDWRO6\PS3URF
68. 'XYLF0:HOVK($-DFNRZ&3DSDGRSRXORV(5HYHLOOH-'$PRV&$QDO\VLVRI+/$'ORFXVDOOHOHVLQ
DORSHFLDDUHDWDSDWLHQWVDQGIDPLOLHV-,QYHVW'HUPDWRO66
 GH$QGUDGH0-DFNRZ&:'DKP1+RUGLQVN\05HYHLOOH-''XYLF0$ORSHFLDDUHDWDLQIDPLOLHV
DVVRFLDWLRQZLWKWKH+/$ORFXV-,QYHVW'HUPDWRO6\PS3URF
 &RORPEH%:3ULFH9+.KRXU\(/*DURYR\05/RX&'+/$FODVV,,DQWLJHQDVVRFLDWLRQVKHOSGHQH
WZRW\SHVRIDORSHFLDDUHDWD-$P$FDG'HUPDWRO
 .DYDN$%D\NDO&2]DUPDDQ*$NDU8+/$LQDORSHFLDDUHDWD,QW-'HUPDWRO
 9DOVHFFKL 5 9LFDUL 2 )ULJHQL $ )RLDGHOOL / 1DOGL / &DLQHOOL 7 )DPLOLDO DORSHFLD DUHDWDJHQHWLF
VXVFHSWLELOLW\RUFRLQFLGHQFH"$FWD'HUP9HQHUHRO
Acta Dermatoven APA Vol 20, 2011, No 4

197

Epidemiologic and genetic characteristics of alopecia areata (part 1)

R e v i e w A r t i c l e

 $NDU$2UNXQRJOX(6HQJXO$2]DWD0*XU$5+/$FODVV,,DOOHOHVLQSDWLHQWVZLWKDORSHFLDDUHDWD
(XU-'HUPDWRO
 0RUOLQJ1)UHQW]*)XJJHU/*HRUJVHQ--DNREVHQ%2GXP1$GQD63RO\PRUSKLVPRI+/$FODVV,,
JHQHVLQDORSHFLDDUHDWD'LV0DUNHUV
 ;LDR)/=KRX)6/LX-%<DQ./&XL<*DR0/LDQJ<+6XQ/'=KRX60=KX<*=KDQJ;-
<DQJ6$VVRFLDWLRQRI+/$'4$DQG'4%DOOHOHVZLWKDORSHFLDDUHDWDLQ&KLQHVH+DQV$UFK'HUPDWRO
5HV
 'XYLF0+RUGLQVN\0.)LHGOHU9&2%ULHQ:5<RXQJ55HYHLOOH-'+/$'ORFXVDVVRFLDWLRQVLQ
DORSHFLDDUHDWD$UFK'HUPDWRO
 'H$QGUDGH0-DFNRZ&0'DKP1+RUGLQVN\05HYHLOOH-''XYLF0$ORSHFLDDUHDWDLQIDPLOLHVDVVRFLDWLRQ
ZLWKWKH+/$ORFXV-,QYHVW'HUPDWRO6\PS3URF
 (QW]3%ODXPHLVHU%%HW]5&/DPEHUW-6H\PRQV.(LJHOVKRYHQ6+DQQHNHQ6.UXVH51UQEHUJ
3 1DJ\ 0 1|WKHQ 00 ,QYHVWLJDWLRQ RI WKH +/$'5% ORFXV LQ DORSHFLD DUHDWD (XU - 'HUPDWRO

 %URQLDUF]\N'\OD*3UXVLVND%UDWR0'XEOD%HUQHU0$UNXV]HZVND&%RURZLHF0.RZDOVNL0/
:RV]F]HN*7KHSURWHFWLYHUROHRIWKH+/$'5ORFXVLQSDWLHQWVZLWKYDULRXVFOLQLFDOW\SHVRIDORSHFLD
DUHDWD$UFK,PPXQRO7KHU([S:DUV]
 2UHFFKLD * %HOYHGHUH 0& 0DUWLQHWWL 0 &DSHOOL ( 5DEELRVL * +XPDQ OHXNRF\WH DQWLJHQ UHJLRQ
LQYROYHPHQWLQWKHJHQHWLFSUHGLVSRVLWLRQWRDORSHFLDDUHDWD'HUPDWRORJLFD
81. 7D]L$KQLQL5&RUN0-:HQJUDI':LOVRQ$**DZNURGJHU'-%LUFK030HVVHQJHU$-0F'RQDJK
$-1RWFKDQRQ+/$JHQHLQWKH0+&LVVWURQJO\DVVRFLDWHGZLWKWKHPRVWVHYHUHIRUPRIDORSHFLDDUHDWD
+XP*HQW
 /HRQJ.*+X;/L/1RVHGD0/DUULYpH%+XOO&+RRG/:RQJ).DUVDQ$$FWLYDWHG1RWFK
LQKLELWVDQJLRJHQHVLVUROHRIEHWDLQWHJULQDFWLYDWLRQ0RO&HOO%LRO
83. 0DF'RQDOG+5:LOVRQ$5DGWNH)1RWFKDQG7FHOOGHYHORSPHQWLQVLJKWVIURPFRQGLWLRQDONQRFNRXW
PLFH7UHQGV,PPXQRO
84. 'HIWRV0/%HYDQ0-1RWFKVLJQDOLQJLQ7FHOOGHYHORSPHQW&XUU2SLQ,PPXQRO
85. /LQ0+/HLPHLVWHU&*HVVOHU0.RSDQ5$FWLYDWLRQRIWKH1RWFKSDWKZD\LQWKHKDLUFRUWH[OHDGVWR
DEHUUDQWGLIIHUHQWLDWLRQRIWKHDGMDFHQWKDLUVKDIWOD\HUV'HYHORSPHQW
86. 7D]L$KQLQL57LPPV-0&R[$:LOVRQ$*,GHQWLFDWLRQRIQRYHOVLQJOHQXFOHRWLGHSRO\PRUSKLVPV
ZLWKLQ WKH 127&+ JHQH DQG GHWHUPLQDWLRQ RI DVVRFLDWLRQ ZLWK 0+& DOOHOHV (XU - ,PPXQRJHQHW


A U T H O R S Abdullateef A. Alzolibani, MD, Associate Professor of Dermatology,

A D D R E S S Department of Dermatology, College of Medicine, Qassim University, P.O.
%R[%XUDLGDK4DVVLP6DXGL$UDELD7HO2IFH
H[W)D[(PDLOD]ROLEDQL#\DKRRFRP

198

Acta Dermatoven APA Vol 20, 2011, No 4