Review lJTok 川 omMe 吋dU 凶 8 6 (artxE 1り)E2~E9(ρ2016)
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Katsuji NISHIMURA and Jun ISHIGOOKA D e p a r t m e n t Pfoyrtaihcys lo， ohcS Mfoenicide ， Tkyoo Women's lacideM ytisrevinU ( A c c e p t e d rebotcO 31)5，102 S y s t e m i c supul sustoemahtyre )ELS( sidetaicossa ithw a hhgi ecnedicni pfocirtaihcys .snoitatsefinam How 同 e v er t， isi unknown whether sihtnoitaicossa si a dtceri ecnueqnseoc afoevitc SLE ， iantceridn epiphenomenon -sa
s o c i a t e d hitw eht esaesid irost ypareht ， aro en 旺tce deatlernu Sot E.L pnIralucitra gnihsiug， nitsid -dioretsocitroc i n d u c e d cirtaihcysp redrosid )PDIC( omrf cirtaihcysporuen snoitatsefinam SLE fo (NPSLE) si dtolsuciffi taht-inilc c i a n s era netfo tughca ni a tcituepareh gnikam-noisiced .amemild The srohtua summarize tnecer erutaretil -er g a r d i n
g ehtlacinilc stcepsa pfocirtaihcys syndromes NPSLE fo nitsartnoc hitw s.DPIC Based londetimi seiduts ， d e l i r i u
m s， isochysp ， and reeves-o-tetaredom evitingoc noitcnufsyd may more eb eivtseggus NPSLEfo yllai， cepse
i n sesac denimpaocca by rksi srotcaf NPSLE fo .g.e( ， deasercni lareneg esaesid ytivitca ， suoiverp stneve ， rehto c o n c u r r e n t NPSLE snoitatsefinam ， proyltnetsisre evitisop dipilohpsohpitna .)seidobitna lyseernvoC ， mood -rosid d e r
s hitw manic/mixed serutaef may more eb evtiseggus CIPDfo yllaic， epse retfa etuca es， od-hgih dioretsocitroc
t h e r a p y
. However ， NPSLE and CIPD nca hotb tneserp ssorca a sumpectr pfocirtaihcys .semordnys ughAltho -er
c e n
t seiduts eavh detsgegus some lufesu noitamrofni taht anc make rof retteb management tfoeseh detacilpomc c o n d i t i o n s lu， ferac citsongaid snoitagitsevni gnidulcni acinilc ，lyrotarobal ， and niarb ginmagi sgnidnif dlouhs be c o n d u c t e d on a cesac-yb-esa .sisab Key W o:sdrdecudni-dioretsocitroc cirtaihcysp sredrosid cirtaihcy， sporuen supul ， cmietsys supul ussotaemyther I n t r o d u c t i o n A vtyeria fo ciogolruen and citraihcysp -nsy dromes lyntueeqfr occur nitsneitap with imcsyste l u p u s erythematosus E)SL( ， a ccniorh and -gnispaler r e m i t t i n g autoimmune myotarmalfni esaseid ト)4 N ecitraihycpsour sniottaesfniam fo SLE (NPSLE) a r e deaticsosa with a neivatge impact on pisosognr ， q u a l i t y foefil ， llarevo damage fo het easesid ， and working tilibasid y.)5 At the same time -ret， socitroc o i d s ， het nestoernroc treatment fo rof SLE ， era -erf q u e n t l y deaticsosa with resveda cirtiahcysp stceffe ， i n c l u d i n g evitceffa sredrsoid ， ciotchsyp serdorsid ， and umiireld 6 )-8). I n ecitacrp ， ti si netfo tluciffid ot hsiugnitsid c o r t i c o s t e r o i d -i n d u c e d cirtaihcyps rdersoid (CIPD) from NPSLE 0191 ) . When SLE stenitap on c-retsocitro o i d
s sentpre new cirtiahcysp symptoms ， an emerg-i
n
g lacinilc dilemma usrcco over whether eth -sod age fosdioretsocitroc dlhuos be ddesaerce ro -ni c r e a s e d . tIn sih review ， we pvidero an overview fo c l i n i c a l sctpesa pfociratihcys syndromes NPSLE fo i n
ctsraton with CIPDs make ot rof retetb manage-ment fo ehest deicatmlopc .snoitidnoc Data -er t r i e v e d rof eth noitcrutsnoc tfo he review were -bo t a i n e
d from two main :sceruos aggregated -refer e
n c e
s taken from entrec eswrive and a PubMed s e a r c h ingcover eht tasp twenty .sraey 図 :ijustaK NISHIMURA tnemtrapeD foyrtaihcysP ， loohcS foenicideM ， okyoT ns'oemW lacideM ytisrevinU ， 8-1 K a w a d a -c h o uk-uku， jnihS ， oykoT 666， 8-261 J anpa E -m a i l : [email protected]
Primary and secondary NPSLE D e s p i t e a high encdeicin pfocirtiahcys -tasfeniam t i o n
s edtiaocsas with SLE ， tisi tno known whether t
h i
s noitaicossa si a dtceri consequence sfo ystemic autoimmunity and noiatmmalfni .g.e( ， entry ifo m
-mune sllec and uelscelom otni eht larntec nervous system ])SCN[ “(primary NPSLE") ， an itceridn e妊cte a s csontiicalpmo tfo he eseasid .g.e( ， uremia hor y -p e r t e n s i o n ) irost therapy .g.e( )sdioretsoc， itroc “(-ces ondary NPSLE") ， an e旺ero tc detalernu SLE ot .g.e( ， i n f e c t i o n s ， colitabem seitialrmonba ， ro adverse m e d i c a t i o n e妊e')Stc ! )-14).1 In 9199 ， eth American -loC l e g e Rheumatology fo (ACR) hcsearer ommitteeωc p u b l i s h e d ecas snoitinifed rof NPSLE 91 syndromes i n c l u d i n g C21 ldeater-SN syndromes and 7 p-hipre e r a
l nervous detaler-metsys syndromes. However ，
t h
enoitacifissalc was tno ylirassecen cificeps rof irp 圃
mary SLE because no dcitsnogai ldgo standard fo primary SLE .detsixe a mIn sisylnaa-ate fo s17 -dut i e s gnitgaistevni NPSLE ngplyiap het 9199 ACR c a s e snoitinifed ， Unterman te 1a4 ) edestimat a-revp l e n c e s tfo eh gnwiollof cirtaichysp syndromes: mood d i s o r d e r (20.7%) ， eviitngoc noictunfsyd 1(9.7%) ， a n x i e t y rdeorisd 6，()%4. sioshcysp )%6.4( ， and uteac c o n f u s i o n a l etats 3(%).4 bleaT( .)1 A legra tyjorima o f eth mood rsdeorsdi fo NPSLE ear nsioresdep w h i l e mania siylrear etnserp ， ginccurro ni -xioprpa mately lyon 3 % o pfstnieta 2 ) . A i n i a l a te la)l conducted a canoitces-ssor ，l-ulppo a t i o n -b a s e d study aot ssses eth ytidilav tfo he ACR nomenclature rof NPSLE. Forty-two 19( %) fo 46 p-a t
i e n t
s and 25 (56%) fo 46 cslrotno matched by age ，
sex ， onatiduce ， and ceapl fo cendesire dellifluf ta l
e a s
t one tfo eh ACR NPSLE .airetirc etvinigoC -sdy f u n c t i o
n was het most common syndrome cteddete i n 7 p3 snteita ).0%8( They found het ngiwlolfo NP e v e n t s tath osla derurcco with high frequency ni normal onatiulopp :slortnoc yetixna ， mild s-reepd s i o n tath( sliaf ot meet eht airetirc rof “major d e p r e s s i v e -l i k e )s"deoisep ， and dilm eivtinogc im 圃
pairment sticifed( ni fewer than eerth tfo eh tghie s p e c i f i e d veitnigoc .)sniamod Based on the stluser from siht study ， they proposed defiidom airetirc rof NPSL .E I n a peivectpsor retnc， e-elgnis torcoh study up fo t o 7 years conducted by Hanly aFte 6 ) ， 213 (63%) fo
209 stnetiap demonstrated ta tsael one NP event ( 2 9 9 svente atot )ldezieratcrahc by teh ACR asec d e f i n i t i o n s ， but nlyo 13 % tfo he latot sevent were -ta t r i b u t e d SLot .E They used noisiced selur gndilucin t h e abovementioned iedodifm airetirc by Aaalini te aF 7 ) determine ot het noitubirtta NP efo s.tnev Fur -thermore ， Hanly ate F 8 ) demonstrated ni an i-anretn t i o n a l niotpceni tohorc study taht 486 fo，1206 -ap t i e n t
s %).304( had ltatsae 1 NP event over a mean f o l l o w -u p fo .19土1. 2 y.srae The ntioorropp fo NP e v e n t s dteubritta ot SLE drieva from yonl 13.0% (most tngenrits model NPSLE) fo ot 23.6% ta( tsael s t r i n g e n
t model fo NPSLE) fo.stneitap The most f r e q u e n t snoitubirtta ot SLE fociratihcysp sevent ( t h e oitar fociratihcysp tsenev detbuirtta ot SLE over eht latot citraihcysp )stneve were seen ni -yps c
h o s i
s ， from 571.% (eht most tnengitrs model fo NPSLE) ot 92.9% eht( tsael ntengitrs model fo T a b l e 1 Edetamist ecnelaverp pcfiortaihcys semordyns ni SLE nda ehtoitar tfoehnoitubirtta ot SLE E s t i m a t e d becnelaverp .oN pfoyramir NPSLE .oN/stneve tfolato NP estnev C)%( P s y c h i a t r i c semordnys a % I%C59 tsoM tnegnirts NPSLE ltAtsae tnegnirts NPSLE Mood redrosid 7.02 1.713-5 4. 931/81 )%9.21( 931/74 )%8.33( C o g n i t i v e noitcnufsyd 7.91 0.63-7.01 34/8)%6.81( 34/22 5(.1)%2 A n x i e t y redrosid 64. 6.31-0.3 24/0 ( 0)% 24/0 ( 0)% P s y c h o s i s 6.4 -24.8.8 41/8 75()%1. 41/31 )%9.29( A c u t e lanoisufnoc etats 34. 1.31.01- 22/11 ( 5)%0 22/71 )%3.77( a D e f i n e d tyb eh naciremA egelloC foygolotamuehR erutalcnemon dna esacsnoitinifed cirrotafihcysporuen supul s y n d r o m e s .)9991( b E s t i m a t e d sis myyblana-ate gnisu e-modnar 旺e'stc ledom Uybnamretn te a，l0102 4). C F r o m lano iintaanretn esaesid noitpecni trohoc SLE fo stneitap Hybylna tela， 0102 18 ). N P S L E : cirtaihcysporuen cimetsys supul susotamehtyre :， ICecnedifnoc avretni .l
-E3-NPSLE); nietuca lanoisufnoc setats ， 50% ot;%3.77 and nievitingoc noitcnufsyd ， %6.81 51ot . 2% ， elihw t h e tsael tneuqerf snoitubirtta SLE ot were nees ni a n x i e t y sredrosid ， 0% t 0%; o and mood ni sredrosid ， 1 2 . 9 % to 8.33 %. (nI siht dyuts ， eht srohtua did ton c h a r a c t e r i z e whether eht mood sredrosid dedulcni d e p r e s s i v e ， manic ， ro mixed .)edosipe ughAltho many cirtaihcysp stneve were detubirtta ot -non SLE sesuca ， soncificep seusac gnidulcni -retsocitroc o i d
s were shown nisiht .yduts bleTa 1 shows eht e s t i m a t e d cenelvaerp focirtaihcysp syndromes d e m o n s t r a t e d ni eht denoitnem-evoba -tame a n a l y s i s foseiduts gnitagitsevni NPSLE gniylpap t h
e 9991 ACR esac snoitinifed 4) and the oitar tfo eh a t t r i b u t i o n ωot SLE shown tnisih ωs坑ydut Based on fsgnidni from evitcepsorp
∞
coho0ぽ2tr)ピ
91ω) and 則0 c a s e -c o n t r o l l 22υ)2山l却2幻)seiduts ， eht European League A g a i n s t Rheumatism (EULAR) hcareser t-micom t e e)3d2eifitnedi major ksir srotcaf rofcirtaihcysp m a n i f e s t a t i o n s fo imarypr NPSLE sa:swollof )1( g e n e r a l esaesid ytivitca fo SLE yllaicepse( rof -es v e r e evitingoc )noitcnufsyd附
へ
)2( suoiverp stenve o r oreht tnerruncoc NPSLE snoitatsefinam 0 )2， and )3( p e r s i s t e n t l y evitisop dipilohpsohpitna seidobitna ( e s p e c i a l l y rofereves-ot-etaredom evitingoc -syd f u n c t i o n ) 2 )l122. C o r t i c o s t e r o i d -i n d u c e d cirtaihcysp rerdoisd ( C I P D ) An eylra egral sisylana-atem ssorca c92lacinil -fe f i c a c y seiduts fdiooretsocitroc ypareht rof lareves m e d i c a l snoitidnoc detarstnomed taht eerves -ysp c h i a t r i c syndromes edrurcoc ni 0%-52 ， a wdightee a v e r a g e 5fo 7%. ， and dlim ot atemoder syndromes i n 2%3-61 ， a wdightee egareva 2fo.)42%8 dingccorA t o ansisylana fodehsilbup esac stroper fo CIPD syndromes ， ereht was mania ni %; d53 noisserpe ni2 8 %; mania and noisserped ni %; d21 muirile ni 13%; and sisohcysp ni 11 % お ) nteecR seiduts )72)62 h a v
e edstgeugs taht mania si eht most commonly o b s e r v e d ensopesr ot etuca ypareht hitw ylevitaler h i g h sesdo fsodioretsocitroc ， elihw noisserped si l i k e l
y more common anth mania gnirud mert-gnlo t r e a t m e n t hitwsdioretsocitroc .7) Moreover sdioretso， citroc eraylgnisaercni -hgih l i g h t e d bsa gine detaicossa thiw evitingocoruen -mi p a i r m e n t .)6 )822 The most ylevisnetxe dertoper -ingoc t i v e seangch gnitluser omrf dioretsocitroc -taert ment evlovni evitaralced )labrev( memory ， and co 剛
c u r r e d ngirdu thbo mret-trohs )esod-hgih( )62 and l o n g -t e r m ylevitaler( )esod-wol )03-)82 seipareht ， -er f l e c t i n g a htnedepn-sdempucaopip ssecrop .)7 -ruF t h e r m o r e ， even ereves evitingoc sredrosid hucs sa d e m e n t i a and muiriled have nbee edtroepr 1 ).3 A rtnece troper from eht UK ungis egral spleams o f erov 073 ，000 stneitap ni a pryimar erac gnittes showed taht eht rdzaah oitar rofladicius roivhaeb i nstneitap detaert thiw sdioretsocitroc was 9.6 ni c o m p a r i s o n potelpoe hitw eht same gniylrednu -sid e a s e s who were ton ;desopxe rof noisserped ， .1;8rof mania ;3， .4 rof muiriled no， isufnoc ， dnrooitatneirosi ， 5.1 ; and rof cinap redrosid ， .12 )53. erargL yliad sesod o f csdioretsocitro ， a proir yrotsih nfo-taihcysporue r i
c sredrosid ， and a psuoiver yrotsih CIPD fo were a s s o c i a t e d htiw a gretaer ksir CIPDfo 2 ).3 rheigH -roc t i c o s t e r o i d esgaosd yl， laicepse 三04 mg/ dya sa p r e d n i s o n e 3 )3， have been demrifnoc nilareves -duts i e s tsa eh most ntatorpim ksir rotcaf rof s.PDIC To desnogai stneitap hsa ngvia CIPD ， eseht -duts i e s aveh been deilppa eht airetirc fo-ecnatsbus i n d u c e d cirtaihcysp sredrosid ni areneg .lFor exam -p l e ， ni modern citsongaid smetssy .， g.e ， eht -eriAm c a n cirtaihcysP s'noitaicossA citsongaiD and -sitatS t i c a l Manual Mfo talen sredrosiD ， ht4 noitide (DSM-I V ) 3 4 l ， eseht sredrosid were denifed fsa:wollo )1( eht p s y c h i a t r i c symptoms edplovede retfa gnriud ， ro w i t h i n a month foecnastbus noitacixotni ro -htiw drawa ，l and )2( noitaicdem esu was yllacigoloite -er l a t e d tot eh.ecnabrutsid The citsongaid airetirc -pa p l i e
d ni ylrae seiduts fo CIPD were eht same ni p r i n c i p l e sa eseht modern .airetirc However ， -epse c i a l l y eniylra seiduts ， desnoagdisim sesac htmig be i n c l u d e d esucabe rehto seigoloite were .dekoolrevo Impact CIPD of on pstneita thwi SLE SLE ash been dertoper osa ne tfo eh ksir srotcaf f o r CIPD tnieh denoitne-mveoba sisylana-atem 4 ).2 nI t h e sisylana ， eht ecnedicni pfocirtaihcys syndromes i nstneitap who deviecer dioretsocitroc yaprhet rof SLE was %2.93 dethgiew( .)egareva The ecnedicni r a t e was yltnacifingis rehgih anth eht %.75 -icni d e n c e nese when llasesaesid ， hsuc sa lymphoma ，
m u l t i p l e sisorelcs evit， areclu sitiloc ， ro idatoeumrh a r t h r i t i s ， were deredisnoc .rehtegot R e c e n
t two trohoc seiduts by Chau and Mok お)
and aimurNish ate1 63 ) datestrmoned eht ecnedicni fo CIPD ni SLE stneitap detaert htwi sdioretsocitroc u s i n g ta scirt noitinifed and evnsiehemproc -songaid t i c euredocpr gnidrocca tot eh DSM-IV airetirc 43 ) . nI b o t h seiduts ， eht common gniwollof tcirts noitinifed o f CIPD was ed:employ tesno-wen cirtaihcysp symptoms taht deopleved nihtiw 8 weeks if-oaitin t i o n aro ionattnemgu cdfiooretsocitro yaperht and t h a t devloser yletelpmoc hguorht a rnoitcude ni c o r t i c o s t e r o i d eagosd and touhitw lanoitidda -mi m u n o s u p p r e s s i v e .stnega
Chau and Mok 却dteroper taht CIPD edrurcoc ni
s i x stneitap (5%) fo a pevitcepsor trohoc 9fo p2 -a t i e n t s hitw SLE retfa ehtnoitaitini cdfiooretsocitro t h e r a p y . Of teh xis stneitap ， eerht dpeoelevd -ysp c h o s i s and eht rehto eerht dpeloeevd mood -rosid d e r s htwi manic .serutaef arumihsiN te 1a63 ) -noc d u c t e d n oalanoitavresb yduts fo 161 evitucesnoc e p i s o d e s ni 515stneitap-ni htiw an SLE eralf who were detaert thiw.sdioretsocitroc retfA noisulcxe o f 2 e2 sedosip thiw nterruc trevo lartnec svouner s y s t e m snoitatsefinam SLE fo )ENS-SLC( ， a d-ongai s i
s CIPD fo was made rof (41 01 1.%) 1fo 39 sedosipe i n 351 stneitap htiw a non-CNS-SLE eralf nihtiw 8 weeks cdifooretsocitro noitartsinimda by a p-aihcys t r i s .tcitohcysP sredrosid derrucco ni eon tenve (7%) ， and mood sredrosid derrcuco ni 31 stnvee (93%) gn， idulcni evisserped serutaef ni two (14%) ，
manic serutaef nnieni 46(，)% and mixed serutaef ni two 41( .%) The ecnedicni CIPDs fo from eseht -duts i e s tmigh be udetmatieserdn esuaceb fo eht tcirts d e f i n i t i o n .desu nI eht rermof ytuds 却 ni which CIPDs were ton detualave by a ptsirtaihcys ， a lrweo i n c i d e n c e CIPDs fo was edtropre nhat ni eht rettal s t u d y)638.4( % vs 101..)% dilM evitingoc noitcnufsyd may osla have been detaimsterednu ni thob seiduts ， b e c a u s e ondeliated stnmessessa gnisu -syprouen c h o l o g i c a l stset were .demrorfep I n ea rvitcepsorte trohoc dytus fo 520 stneitap w i t h SLE ， rleelzenppA te)7Padeifitnedi etuca -ysp c h o s i s ni (17%)98 ， which fo eht lasuac breakdown was imarypr CNS tnemevolvni ni 95 ， CIPD ni 82 ， and unknown ni .owt sisochysP due ot aryprim NPSLE dtaesaesi tesno n(
=
)91 was detaicossa hitw d i s e a s e ytivitca ， sisohcysp due ot yrimarp NPSLE d u r i n g pu-wollof SLE fo n(=
)04 was detaicossa thiw p o s i t i v e dipilohpsohpitna seidobitna and ssel -erf q u e n t l y thwi laner and suoenatuc nemelvovni ，t and t e n 2fo p8stneita thwi CIPD had aoalbuminemihyp when sisohcysp .depolevedRisk rsotcaf orf CIPD pnistneita thwi SLE Hypoalbuminemia sah enbe dettarnsomed bot e a r i s k rotcaf rof CIPDs ni SLE stneitap 53 ) 3 8 ) ， utb eht p r o p o s e d mechanism sinmare .evitaluceps nI eht a b o v e -m e n t i o n e d evitcepsorp dytus by Chau and Mok 35 )， hguohlta ksir srotcaf rof CIPD dedulcni low
serum slevel fo nimubla ， complemen ，t and -erc
a t i n i n e ， a hyrotsi afoyteixn sredrosid ， and a fylima h i s t o r y pfocirtaihcys sessenlli ， ylno e-nimulbpoahy mia demainer tnacifingis retfa etairavitlum -tsujda men .t I n gaeren ，lniarb damage droesaesi any fo loite 剛 ogy may esopsiderp a pnsore otdecudni-ecnatsubs p s y c h i a t r i c sredrosid chus sa muiriled .)93 lareveS s u b c l i n i c a l CNS-SLE sgnidnif .g， .e ， mlaoranb -ortcele e n c e p h a l o g r a m G)EE( ， citengam encnaoesr ingimag ( M R I ) tfoeh niarb ， crolanipsorbere diulf )FCS( dnif 田 i n g s ， era deversbo ni SLE stneitap ， sseldrager fo whether yeht tibihxe tnerruc trevo NP symptoms 9 ) . T h i s lacinilc srolacinilcbu CNS tneemlvovni due ot SLE tmigh esopsiderp a ptneita Cot PD.I -E5-I n teh evitcepsorp dyust 1fo 35 stneitap hitw -non CNS-SLE eralf by Nurashimi te la円evitisop -Q a l b u m i n (CSF /serum numilba ;oitar n iarotacidn fo b l o o d -b r a i n reirrab ]BB[B )egamad and e-mplocoyph mentemia were deifitnedi isa tenndpeden ksir -caf t o r s rof CIPDs gnisu a melpitlu citsigol noisserger a n a l y s i s . evitisoP minbula-Q was detceted niylraen h a l f eht CIPD sedosipe wro thi evitca CNS-SLE ， -la t h o u g h compared hitw sedosipe which ni no p-ihcys a t r i c stneve depoleved s， level fo minbualQ- were h i g h e r tni eh CIPD sedosipe ， and even rehigh ni-ca t i v e CNS-SLE .sedosipe The srohtua detaluceps t h a t BBB damage ightm aebdetaicoss thwi NPSLE and CIPD ， hguothla no lasuac sknil have nbee p r o v e n .
T a b l e 2 elbissoP lamordnys sesongaid otpleh ni d i s t i n g u i s h i n g CIPD morf NPSLE
More common NPSLE ni
A c u t e lanoisufnoc /etatsmuiriled P s y c h o s i s C o g n i t i v e noitcnufsyd etar， edom otereves L e s s common NPSLE ni A n x i e t y redrosid M o o d redrosid evisser， ped edosipe d， lim
More common CIPD ni
M o o d redrosid dexim/c， inam edosipe a E s p e c i a l l y retfa etuca esod-h， gih dioretsocitroc .ypareht C I P D :i-dioretsocitroc n d u c e d cirtaihcysp redrosid ， :ELSPN n e u r o p s y c h i a t r i c cimetsys supul.susotamehtyre NPSLE dregegrit by c?sdioretscoitro The noitautis siosla detcaiplmoc by teh -iripme c a l l y wnwell-kno tcaf taht tnesoe-wn NP symptoms i n SLE stneitap on csdioretsocitro dluco be due ot CNS. 圃SLE and tno a CIPDot
9 ) . A review 1fo 0 sesac o f etcua CNS snoitcailpmoc ni SLE stneitap retfa c o r t i c o s t e r o i d eslup yrapthe showed taht issochysp o c c u r r e d ni ruof stneitap ， seruzies ni eerth ， and h e m i p l e g i a ni ruof 40 ) . Although siht ecnreurcco fo n e u r o l o g i c syndromes edestggus sngis fo NPSLE ， t h e r e was elttil lacigoloisyhpohtap noitarmofni ni t h i s .weiver Tabata ate1 4 1 )edrtoepr ca pirtaide SLE c a s e who showed CNS snoitatsefinam nihtwi 2 days a f t e r dioretsocitroc eslup .ypareht Both tfoeseh -er p o r t s ， however ， showed ylno a clacigolonorh -aler t i o n s h i p between dioretsocitroc noitartsinimda and p s y c h i a t r i c .snoitatsefinam I n teh lanoitavresbo ytuds by Nishimura te la叫， d u r i n g eht 8 weeks cfdoioretsocitro noitartsinimda ， new cirtaihcysp sntvee rdecruco 2ni 0 (41 4.%) tfo eh 1 3 9 sdeosiep ni 531 stneitap ithw a non-CNS-SLE f l a r e . Of teh 0 p2stneita ， two .1( 4 %) were dsenoiagd a
s CNS-SLE ， and othb detneserp .muiriled Even
p r i o r ot eht cirtaihcysp snoitatsefinam ， both -ap t i e n t
s had ydarela shown abnormal sgnidnif -gus g e s t i n g CNS involvemen ，t.g.e ， EEG esitilamronba ( d i f f u s e .)gniwols llA tfo eseh sgnidnif improved ni p a r a l l e l thiw eht'stneitap seirveocer through -gua m e n t a t i o n fo immunosuppressive .ypareht sThi s t u d y tsesggus taht dioretsocitroc ypareht sreggirt CIPD and CNS-SLE nistneitap hitw SLE. muriliDe may be sevtiseggu CNS-SLEfo ， leihw mood -rosid
d e r
s thiw manic/ mixed serutaef may be more -gus g e s t i v e CIPDfo 3制 2 ) D i a g n o s t i c and ctieuaprhet sonitaredsinoc forNPSLE Because tfo eh necesba a dfo citsongai dlog -nats d a r d rof NPSLE and seuaceb sforalimi irolacitned p s y c h o p a t h o l o g y thiw CIPD ， eht sisongaid fo-irp mary NPSLE dulosh be adveeihc ylegral by a p-cor e s s efonoisulcx sfo yradnoce oro reht essauc NP fo m a n i f e s t a t i o n s and dlouhs be ddeivre from a clufera a n a l y s i s tfo eh acinilc ，lyrotraobal ， and g-imaeuron i n g atad on a cesac-yb-esa sisab 凶)32 The citsongaid snoitagitsevni rof NPSLE tsisnoc o f teh:gniwollof )1( measurement afoseidobitnaotu ( e . .g， anoureintna ，llamosobiritna P， and -sohpitna p h o l i p i d ;)seidobitna )2(sisylana fo CSF ot deuclex i n f e c t i o n ， ssessa eht BBB noitcnuf ， and measure a u t o a n t i b o d i e s ， yraotmmalfni soriatedm and -arged d a t i o n ;snietorp )3( EEG ;tnemsssesa )4( y-sopuren c h o l o g i c a l assessmen ;t)5( agnigimrouen eotetaulav b r a i
n erutcurts (computed tomography CT][ ， MRI ，
m a g n e t i z a t i o n refsnart igngami [MTI] -no， isuffid w e i g h t e d image [DWI] rosnet-， noisuffid imaging [ D T I ] ) and niarb noitcnuf nortisop( onisisme -ot mography [PET] e， lgnis notohp niosisme computed tomography [SPECT] ， ectingam ecansoner -ceps t r o s c o p y [MRS] ， and lanoitcnuf MRI) .)41 citsonagiD v a l u e s rof NPSLE rof each tset and tenatmret fo NPSLE eraelbaliava onireht ewrevi selcitra 31 )1仰 R e c e n t seiduts tseggus taht eht ngitneesrp -inilc c a
l syndrome may pleh nignihsiugnitsid NPSLE from .IPDC muriileD etuca( lanoisufnoc )etats ， psy 圃 c h o s i s ， and eervse-o-teatredom evitingoc -cnufsyd t i o
n may be more evtisgegsu fo NPSLE 6 )11)8， -epse
c i a l l y ni sseac accompanied by ksir srotcaf rof NPSLE .g.e( ， edsarecni lraeneg esaesid ytivitca ， -erp v i o u s sntvee oro reht tnerurcnoc NPSLE -atsefinam t i o n s ， proyltnetsisre evitisop dipilohpsohpitna -itna b o d i 託sザe
r
玖9mixed serutaef may be more evistegugs ぱ0fCαIPD ，
e s p e c i a l l y retfa eutca se， od-high dioretsocitroc -reht apy elbaT( )27)2 仰 3却5)日附)制
Management of CIPD SLE ni stneitap Because fo eht ycneddepen-esod on c-retsocitro o
i d
s rof eht development CIPDfo 制， CIPD -iteroeht
c a l l y dulhos be tdetare ithw sedo onictudre dro-si c o n t i n u a t i o n tfo eh .gurd Lewis ate F 4l dteorepr taht c l i n i c a l ryecover from CIPD rdecruco ni 4 % o9 3f 6 c a s e s dteaert thwi lyimps gnirpeat eht-retsocitroc o i d .egasod tnI eh sesac thwi SLE l， la CIPDs 41 -co c u r r i n g ni a pevticespor trohoc 1fo 53 SLE stneitap r e s o l v e d lytelempoc retfa dioretsocitroc agedos -er d u c t i o n a mean ot 3fo5.2 mg/ day egnar( ， 54-51 mg/ d a y ) a mean ro 0fo96. mg/kg/ day egnar( ， 2.08幻.0-7 銘8 mgダ/kg ダ/d白ay刊7今)aおs penoloisnder ♂)ω3泌紛6
Psy 戸7氾cho 叩pha 訂rma 舵cC
∞
igolo symptomatic entatmtremay be redirque depending on teh ytireves 0ぱfCIPD
O ぽr the tnemtaert 0ぱf SLE flesti ylra， lucitrap fi sedo r e d u c t i o n dronoitaunitnocsi cfsodioretsocitro si-mi p o s s i b l e . However ， encdeive rof eht psychopharma-c o t h e r a p
y CIPD fo sha been very detimil with seac r e p o r t
s ， a few llams easc seires ， and a few llams
c l i n i c a l .l34l8slairt
For both ciothcsyp and manic/ mixed sedsoipe fo CIPD ， lareves scitohcyspitna odirepolah( ，l-irepsir done ， enipazanlo ， ro)enipaiteuq and mood -zilibats e r s muihtil( ， etaorplav ， zeniperamabac ， lro-girtoma i n e
) have been ylevitceffe used nilareves seac -er p o r t s l8制 . a cnI seires-esa dertpoer by Dsavi te 1 4a
ぺ
t r e a t m e n t lfoesod-wo scitohcyspitna devloser -ysp c h o t i c symptoms 8ni % o3 pfstneita 42( tuo 2fo 9 p-a t i e n t s) and edvolser symptoms nihitw 2 weeks ni 80% pfo.stneita a 5-week nI lebal-nepo lairt ofo-nal z a p i n e 02-5.2 mg/ day (mean 5.8 mg/ d)ya ， 11 tfo eh 1 2 tsneitaptuo thiw manic ro mixed esdoispe fo CIPD showed marked improvement ithw no change eniladaimrypartx edis モ旺tce selacs ， weight ， o r gesoucl measurements 5 ).4 a cnI seires-esa tudys fo r i s p e r i d o n e tni eh mtnetaert CIPD fo ithw manic ro mixed serutaef snixi lemaef stneitap-ni with SLE 6 )4， marked ssenevitceffe rfoenodirepsi pu( ot a mean o f 30. mg/ d;ya geran ， 9-1 mg/ d)ya was rdevbeso ni a l l stneitap ylralucitrap ni eht tsrif 2 w.eeks Except f o r noiatdes one ni tneitap and dilm msinonsikraP ni one neitap ，tllarevo eshet xis stneitap detarelot r i s p e r i d o n e llew thouwit ciolbatem edis e旺stce 6 )4，-la though combining noitarnee-gndoces scitohcyspitna such rsaenodirepsi ， eniapznalo ， qroeniapiteu ithw c o r t i c o s t e r o i d s dlouc show an evitidda tceffe ni terms mfocliobate syndrome. -E7-Use focilcycirt stnasserepditna (TCAs) rof c o r t i c o s t e r o i d 園ducedin noisserped sha been -ruocsid
aged auseecb TCAs netfo etaerbacxe rieht symp-t o m s 8 ) )34. Meanwhile luf， sseccus esu sfoevitcele -ores t o n i n keuptaer srotibihni enitexoulf( ro)enilartres and nniotores enriphnepieron ekatpuer srotibihni ， such saenixaflanev ， have been estedsugg ni esac r e p o r t s ， but no clacinil slairt have been .edtucdonc L i t h i u m sah been dsteeggus saevitceffe rof thbo manic and veissepred sedosipe fo CIPD snilareve c a s e stroper .)348) C o n c l u s i o n s and eurfut snoitecrid
The laitnereffid sisongaid NPSLE fo and CIPD er 町
mains gnginellahc ni.ecitcarp Recent seiduts -gus g e s t muiriled etuca( lanoisufnoc )etats ， ssiochyps ， and ereveso-t-etraedom evitingoc noticunfsdy may be more evtiseggsu NPSLEfo 山)0山-)6 山)2ylla，icepse i n sesac accompanied by ideasercn lareneg esaesid a c t i v i t y ， suioevrp tsenev ， rehot trencurcon NPSLE m a n i f e s t a t i o n s ， royltnetsisrep evitisop -sohpitna p h o l i p i d seidobitna
一
ゆ
~
yleservnoC ，mood sredorsid w i th manic/ mixed serutaef may be more -esgugs t i v e CIPDfo ylla， icepse retfa etuac ， esdo-hgih -itroc c o s t e r o i
d rapyhet ))6224))763)5幻3) However ， NPSLE and
CIPD anc hbot tneesrp ssorac a spectrum pfo-ihcys a t r i c s.ndromesy yllaicepsE ni sesac gnitibihxe -ed l i r i u m mroereveso-t-etardeo evitingoc noitcnufysd ， o t h e r sseauc .， g.e noit， cefni mro ciolbate -ilmarnoba t i e s ， ldoush be e.dedulcx Thus l， uferac citsongaid -ni v e s t i g a t i o n s gnidulcni acinilc ，lyroatrobla ， and niarb i m a g i n g sgnidnif dulhos be ctdeocudn on a cyb-sea 圃 c a s e sisab ot enmierted eht tseb lasuac noitubirtta f o
r cirtaihcysp syndromes ni SLE .stneitap Addi 回
t i o n a l and regral dellortnoc seiduts era needed ot c l a r i f y het ssieneogthap focirtaihcysp syndromes due bot oth NPSLE and CIPD ottucrtnsoc an a-ed q u a t e idla旺itnere management ygetatrs rof eseht c o m p l i c a t e d .snoitidnoc The srohtua troper o fnlaicnani ororeht pihsnoitaler r e l e v a n t toteh stcejbus tfosih.elcitra R e f e r e n c e s 1 ) alainiA H， lakoukoL Jalo， tleP J e at:l The -averp l e n c e cirtfaihocysporuen seomrdnsy nicimetsys l u p u s .susotamehtyre ygolorueN :75 005-694 ， 1002
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) ACR Ad Hoc Committee on Nctriiacyhpsuroe
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) Brown ES ， Chamberlain W ， Dhanani N e alt : An o p e n lebal lairt foenipaznalo rof-dioretsocitroc i n d u c e d mood symptoms. J tceffA drsoiD :38 7-27 2 8 1 ，0420 4 6 ) Nishimura K， Omori M ， toSa E e at:l eondierpsRi i n eht tentmeatr decfudnio-dioretsocitroc mood d i s o r d e r s ， manic/mixed sedosipe niicmtessy suplu e r y t h e m a t o s u s : a cesa seires .yduts Psychosomat 開 i c s :35 93-2928 ， 2012 神経精神ループスとステロイド誘発性精神障害ー精神医学の観点から 東京女子医科大学医学部精神医学講座 西 村 勝 治 ・ 石 郷 岡 純 全 身 性 エ リ テ マ ト ー デ ス cemitsy(s slupu erythematosus : SLE) は 頻 繁 に 神 経 精 神 病 変cirtaihcysporuen(
SLE: NPSLE) を合併する.しかしそれらが活動性の SLE に直接由来するものなのか， SLE やその治療に間接的
に関連するものなのか，あるいはSLE とは無関係の作用によるものなのか十分知られていない.特にステロイ ド誘発性精神障害decudnid-ioertoscirto(c critiahcsyp errdsodi : CIPD) との鑑別はしばしば困難であり，治療に 難渋することも稀ではない.本稿では NPSLE とCIPD の臨床的側面に関する文献のレビューを行った.エビデン スは限られているが，せん妄，精神病性障害，中等度から重度の認知機能障害の場合，特にNPSLE の危険因子 (全般性の疾患活動性の充進， NPSLE の既往歴，他のNPSLE 症状の併発，抗リン脂質抗体の持続陽性)を有して いれば， NPSLE であることがより示唆される.一方，操病あるいは混合性の特徴を伴う気分障害の場合，特に急 性，高用量のステロイド治療後に生じたときにはCIPD であることがより示唆される. しかしながら， NPSLE とCIPD とはいずれも同じスペクトラムの精神症候群を呈しうる.このため基本的にはケース・バイ・ケースに ラボデータ(血清および髄液)や脳画像を含む慎重な鑑別診断を行うべきである.
