Burden of Dermatitis Herpetiformis
Comparison to Coeliac Disease
CAMILLA PASTERNACK
Tampere University Dissertations 68
7DPSHUH8QLYHUVLW\'LVVHUWDWLRQV
&$0,//$3$67(51$&.
%XUGHQRI'HUPDWLWLV +HUSHWLIRUPLV
$&$'(0,&',66(57$7,21 7REHSUHVHQWHGZLWKWKHSHUPLVVLRQRI
WKH)DFXOW\&RXQFLORIWKH)DFXOW\RI0HGLFLQHDQG+HDOWK7HFKQRORJ\
RI7DPSHUH8QLYHUVLW\
IRUSXEOLFGLVFXVVLRQLQWKHDXGLWRULXP) RIWKH$UYREXLOGLQJ$UYR<OS|QNDWX7DPSHUH
RQ-XQHDWR¶FORFN
$&$'(0,&',66(57$7,21
7DPSHUH8QLYHUVLW\)DFXOW\RI0HGLFLQHDQG+HDOWK7HFKQRORJ\
)LQODQG
7DPSHUH8QLYHUVLW\&HOLDF'LVHDVH5HVHDUFK&HQWHU)LQODQG
7DPSHUH8QLYHUVLW\+RVSLWDO'HSDUWPHQWVRI,QWHUQDO0HGLFLQHDQG'HUPDWRORJ\
)LQODQG
3URIHVVRU.DWUL.DXNLQHQ 7DPSHUH8QLYHUVLW\
)LQODQG
'RFHQW7HHD6DOPL
7DPSHUH8QLYHUVLW\
)LQODQG
'RFHQW/DXUD+XLODMD 8QLYHUVLW\RI2XOX )LQODQG
'RFHQW'DQLHO$JDUGK /XQG8QLYHUVLW\
6ZHGHQ
3URIHVVRU0DUNNX9RXWLODLQHQ
8QLYHUVLW\RI7XUNX )LQODQG
7KHRULJLQDOLW\RIWKLVWKHVLVKDVEHHQFKHFNHGXVLQJWKH7XUQLWLQ2ULJLQDOLW\&KHFN VHUYLFH
&RS\ULJKWDXWKRU
&RYHUGHVLJQ5RLKX,QF
,6%1SULQW ,6%1SGI ,661SULQW ,661SGI
KWWSXUQIL851,6%1
3XQD0XVWD2\±<OLRSLVWRSDLQR 7DPSHUH
@@@
*+)+
F<C@8:;@J<8J<@J8E@DDLE<D<;@8K<;;@J<8J<@EN?@:?;@<K8IP>CLK<E:8LJ<JJD8CC 9FN<C DL:FJ8C ;8D8>< @E ><E<K@:8CCP JLJ:<GK@9C< @E;@M@;L8CJ F<C@8: ;@J<8J< N8J GI<M@FLJCP :FEJ@;<I<; KF 9< D8@ECP 8 D8C89JFIGK@FE ;@JFI;<I N@K? FM<IK
>8JKIF@EK<JK@E8CJPDGKFDJ 9LK:LII<EKCP8N@;<I8E><F=<OKI8@EK<JK@E8CJPDGKFDJ 8I<@E:I<8J@E>CPJ<<E <ID8K@K@J?<IG<K@=FID@J $@J8:LK8E<FLJD8E@=<JK8K@FEF=
:F<C@8:;@J<8J<GI<J<EK@E>@E8GGIFO@D8K<CPF=:F<C@8:;@J<8J<G8K@<EKJ%E $
>CLK<E@E;L:<J8E@EK<EJ@M<CP@K:?P8E;9C@JK<I@E>I8J? 8E; $G8K@<EKJ8;;@K@FE8CCP
?8M<M@CCFLJ8KIFG?PFI:F<C@8:KPG<@E=C8DD8K@FE@EK?<JD8CC9FN<CDL:FJ8FK?
;@JFI;<IJ8I<KI<8K<;N@K?8C@=<CFE>>CLK<E=I<<;@<K N?@:??<8CJK?<JD8CC9FN<C :?8E><J8E;K?< $I8J?
1EKI<8K<;:F<C@8:;@J<8J<G8K@<EKJJL==<I=IFD@DG8@I<;HL8C@KPF=C@=<:FDG8I<;
KF K?< ><E<I8C GFGLC8K@FE 3@K? >CLK<E=I<< ;@<K8IP KI<8KD<EK HL8C@KP F= C@=<
@DGIFM<J 9LK=FCCFN@E>8JKI@:K>CLK<E=I<<;@<K@J:?8CC<E>@E>)FI<FM<I 8ELD9<I F=:FDGC@:8K@FEJ8I<8JJF:@8K<;N@K?:F<C@8:;@J<8J< FE<F=N?@:?@J<C<M8K<;I@JB=FI 9FE<=I8:KLI<J"FIK?<J<I<8JFEJ8E;:FDG8I<;KF><E<I8CGFGLC8K@FE K?<;@J<8J<
9LI;<EI<C8K<;KF:F<C@8:;@J<8J<G<IJ@JKJ8E;K?<HL8C@KPF=C@=<@DG8@I<;8DFE>CFE>
K<ID KI<8K<; :F<C@8: ;@J<8J< G8K@<EKJ <JG@K< K?< F9J<IM<; 9LI;<E F= @CCE<JJ 8JJF:@8K<;N@K?:F<C@8:;@J<8J< patients’ perceGK@FEJF=?<8CK? N<CC9<@E>8E;HL8C@KP F=C@=<@E $?8M<9<<EM<IPC@KKC<JKL;@<;
0?@J;@JJ<IK8K@FEJKL;@<JK?<9LI;<EI<C8K<;KF $%E/KL;P HL8C@KPF=C@=<8E;
J<C=G<I:<@M<; <OG<I@<E:<J N<I< <M8CL8K<; GIFJG<:K@M<CP @E $ G8K@<EKJ 8K K?<
K@D<F=K?<;@8>EFJ@J8E;8=K<IFE<P<8IFE8>CLK<E=I<<;@<K%E8;;@K@FE K?<LJ<F=
D<;@:8K@FE8E;?<8CK?:8I<J<IM@:<J;LI@E>K?<P<8IGI<:<;@E>8E;K?<P<8I=FCCFN@E>
K?<;@8>EFJ@JN<I<@EM<JK@>8K<;"LIK?<I K?<<==<:KF=>8JKIF@EK<JK@E8CJPDGKFDJFE K?< 9LI;<E N8J 8JJ<JJ<; /KL;P <M8CL8K<; HL8C@KP F= C@=< 8E; GI<J<E:< F=
>8JKIF@EK<JK@E8C JPDGKFDJ@E CFE>K<ID KI<8K<; $ G8K@<EKJ :FDG8I<; KF CFE>K<IDKI<8K<;:F<C@8:;@J<8J<:FEKIFCJ8E;?<8CK?P:FEKIFCJ
0?<J<C=I<GFIK<;9FE<=I8:KLI<JN<I<:FDG8I<;9<KN<<E $G8K@<EKJ8E;
:F<C@8: ;@J<8J< :FEKIFCJ 8E; =LIK?<I =8:KFIJ 8JJF:@8K<; N@K? =I8:KLI<J N<I<
<M8CL8K<; /KL;P C8I>< I<>@JK<I98J<; ?FJG@K8CKI<8K<; =I8:KLI<J JKL;P
@M
=F:LJ@E>JG<:@=@:8CCPFE?@G=I8:KLI<J @E:CL;<;CFE>K<IDKI<8K<; $G8K@<EKJ 8E; CFE>K<IDKI<8K<;:F<C@8:;@J<8J<:FEKIFCJ/KL;P
0?<;8K8@E/KL;@<J8E;N<I<>8K?<I<;N@K?HL<JK@FEE8@I<J;<J@>E<;=FIK?<
GLIGFJ<F=<8:?JKL;P8E;@E/KL;P9P@EK<IM@<N-L8C@KPF=C@=<N8J8JJ<JJ<;N@K?
K?< ,JP:?FCF>@:8C #<E<I8C 3<CC9<@E> /KL;@<J–8E; N@K? /?FIK=IFD HL<JK@FEE8@I<J/KL;P/<M<I@KPF=>8JKIF@EK<JK@E8CJPDGKFDJN8J8JJ<JJ<;N@K?
K?<#8JKIF@EK<JK@E8C/PDGKFDJ.8K@E>/:8C<HL<JK@FEE8@I<@E/KL;@<J8E;0?<
*8K@FE8C$FJG@K8C @J:?8I><.<>@JK<IN8JLJ<;@E/KL;P
0?< $G8K@<EKJN<I<J?FNEKF?8M<@DG8@I<;G<I:<GK@FEJF=K?<@I?<8CK?8E;
GFFI<IHL8C@KPF=C@=<8KK?<K@D<F=K?<;@8>EFJ@J:FDG8I<;KFK?<?<8CK?P:FEKIFCJ
"LIK?<I $ G8K@<EKJ N@K? >8JKIF@EK<JK@E8C JPDGKFDJ N<I< J?FNE KF ?8M< CFN<I HL8C@KP F= C@=< 8K ;@8>EFJ@J :FDG8I<; KF K?FJ< N@K?FLK >8JKIF@EK<JK@E8C JPDGKFDJ ,#3KFK8CD<;@8EMJ $FN<M<I 8=K<IFE<P<8I’s8;?<I<E:<KF 8>CLK<E=I<<;@<K HL8C@KPF=C@=<@E $G8K@<EKJN@K?8E;N@K?FLK>8JKIF@EK<JK@E8C JPDGKFDJN8JJ?FNEKF9<:FDG8I89C<KFK?8KF=?<8CK?P:FEKIFCJ(@B<N@J<K?<
HL8C@KPF=C@=<F=CFE>K<IDKI<8K<; $G8K@<EKJ;@;EFK;@==<I=IFDK?8KF=:FEKIFCJ ,#3KFK8CD<;@8EMJ 8E;KI<8K<; $G8K@<EKJN<I<J?FNE EFKKFJL==<I=IFDG<IJ@JK<EK>8JKIF@EK<JK@E8CJPDGKFDJ0?<J<C=I<GFIK<;C@=<K@D<
9FE<=I8:KLI<I@JBN8JJ@D@C8I@E $8E;:F<C@8:;@J<8J< 9LKK?<=I8:KLI<I@JB8=K<I $FI:F<C@8:;@J<8J<;@8>EFJ@JN8JCFN<I@E=<D8C< $G8K@<EKJ K?8E@E=<D8C<
:F<C@8:;@J<8J<:FEKIFCJ?8Q8I;I8K@F $. :FE=@;<E:<@EK<IM8C %–
0?< $G8K@<EKJ8E;:F<C@8:;@J<8J<:FEKIFCJN@K?=I8:KLI<JI<GFIK<;DFI<
J<M<I< I<=CLO JPDGKFDJ 8E; LJ<; GIFKFEGLDG @E?@9@KFI D<;@:8K@FE DFI< F=K<E K?8E K?FJ< N@K?FLK =I8:KLI<J 0?< I@JB F= ?FJG@K8CKI<8K<; =I8:KLI<J 8=K<I 9<@E>
;@8>EFJ<;N8J=FLE;KF9<CFN<I@E $K?8E@E:F<C@8:;@J<8J<$. % – 9LKK?<?@G=I8:KLI<@E:@;<E:<I8K<J@E9FK? $8E;:F<C@8::F?FIKJN<I<
:FDG8I89C<KFK?FJ<@EK?<><E<I8CGFGLC8K@FEF="@EC8E;
0?<GI<J<EKJKL;PJ?FN<;8E@E:I<8J<;9LI;<EI<C8K<;KFLEKI<8K<; 9LKEFKKF J?FIK8E;CFE>K<IDKI<8K<; $"LIK?<I K?<GI<J<E:<F=>8JKIF@EK<JK@E8CJPDGKFDJ 8KK?<K@D<F=;@8>EFJ@J?8;8J@>E@=@:8EK@DG8:KFEK?<9LI;<E 9LKCFE>K<IDKI<8K<;
$G8K@<EKJN<I<J?FNEEFKKFJL==<I=IFDG<IJ@JK<EK>8JKIF@EK<JK@E8CJPDGKFDJ
=K<I;@8>EFJ@J 9FE<=I8:KLI<I@JB@E:F<C@8:;@J<8J<J<<D<;KF9<?@>?<IK?8E@E $/LIGI@J@E>CP ?@G=I8:KLI<I@JBN8JJ?FNEEFKKF9<@E:I<8J<;@E $ EFI@E :F<C@8:;@J<8J< N?@:?@E<8IC@<IJKL;@<J?8J9<<EC@EB<;KF@E:I<8J<;?@G=I8:KLI<I@JB
M
+ - *+#$M
'<C@8B@8FE@DDLLE@MWC@KK<@E<EJ8@I8LJ AFJJ8I8M@EEFE>CLK<<E@8@?<LKK88F?LKJLFC<E C@D8B8CMFEM8LI@FE><E<<KK@J<JK@8CKK@@CC8PBJ@C_@CCW@<DD@EB<C@8B@8@CD<E@GWWFJ@E M8@B<@E8M8KJ8F@I<@E8A8@D<PKPD@J?W@I@_EW DLKK8EPBPWWEP?WLJ<8DD@EB<C@8B@88 J8@I8JK8M8K BWIJ@MWK <I@C8@J@JK8 JLFC@JKFE LCBFGLFC@J@JK8 F@I<@JK8 %?FB<C@8B@8JJ8 B<C@8B@8E @?F@CD<EKPDWJJW I8M@EEFE >CLK<<E@ 8@?<LKK88 BLK@J<M8E A8 I8BBLC8@J<E
@?FKKLD8E)P_J@?FB<C@8B@88J8@I8JK8M@CC8KF;<K88EF?LKJLFC<JJ8B<C@8B@8CC<KPPG@CC@J@W DLLKFBJ@8 DLKK8 LJ<@E C@<M<DG@8JK<@J<E8 BL@E BC8JJ@J<JJ8 B<C@8B@8JJ8 %?FB<C@8B@88
<J@@EKPP EF@E B<C@8B@8GFK@C8@JK8 /<BW B<C@8B@88 <KKW @?FB<C@8B@88 ?F@;<K88E
<C@E@BW@J<CCW >CLK<<E@KKFD8CC8 ILFB8M8C@FCC8 AFB8 G8I8EK88 F?LKJLFC@M8LI@FE J<BW
@?FB<C@8B@88EC@@KKPMWE@?FKKLD8E
@8>EFFJ@M8@?<<JJ8 B<C@8B@8GFK@C88K BWIJ@MWK 8C<EKLE<<JK8 <CWDWEC88;LJK8 A8 BWPKKWMWKK<IM<PJG8CM<CL@K8A8CWWBB<@KWMW<JK_W<E<DDWE.LFB8M8C@F?F@;FEDP_KW K8LK@K88BB8MW?<E<< DLKK8;@<<K@EEFL;8KK8D@E<EFE?88JK8M88(@JWBJ@B<C@8B@88E C@@KKPPBFDGC@B88K@F@K8 AF@JK8PBJ@FEC@JWWEKPEPKI@JB@CLLEDLIKLD@CC<*W@JKWJP@JKW
?F@;<KKLLEB@EB<C@8B@88EC@@KKPPC@JWWEKPEPKKWK8LK@K88BB88A8<CWDWEC88KLFE8C<EKLELK M<II8KKLE8 EFID88C@MW<JK__E '<C@8B@88E C@@KKPMWJKW K8LK@K88B8JK8 ?LFC@D8KK8
@?FB<C@8B@88EC@@KKPMWWK8LK@K88BB88A8<CWDWEC88KL8<@FC<ALLI@B88EKLKB@KKL
0WDWMW@K_JB@IA8KLKB@@@?FB<C@8B@88EC@@KKPMWWK8LK@K88BB88+J8KP_JJWKLKB@KK@@E @?FB<C@8B@8GFK@C88E <CWDWEC88KL8 A8 BFB<DLBJ@8 K<IM<P;<JKW ;@8>EFFJ@?<KB<CCW J<BWMLF;<EB<JKWE<<E>CLK<<E@KKFD8EILFB8M8C@F?F@;FEAWCB<<E(@JWBJ@M<II8KK@@E K<IM<PJG8CM<CL@;<E A8 CWWBB<@;<E BWPKK_W MLFKK8 <EE<E A8 AWCB<<E ;@8>EFFJ@E A8 B8IKF@K<KK@@E M8KJ8F@I<@;<E M8@BLKLJK8 K8LK@K88BB88E +J8KP_JJW KLKB@KK@@E G@KBWWE ILFB8M8C@F?F@;FCC8 FCC<@;<E @?FB<C@8B@8GFK@C88E <CWDWEC88KL8 A8 BF<KKLA8 M8KJ8F@I<@K8M<II8KKLE8G@KBWWEILFB8M8C@F?F@;FCC8FCC<<J<<EB<C@8B@8M<IIFBB@@EA8 K<IM<<J<<EM<IIFBB@@E
,FK@C8@;<E @KJ<@CDF@KK8D@8 DLIKLD@8 M<II8KK@@E @?FB<C@8B@8GFK@C88E A8 B<C@8B@8M<IIFB@E MWC@CCW A8 DLIKLD@@E C@@KKPM@W K<B@A_@KW B8IKF@K<KK@@E +J8KP_
%JFJJ8 I<B@JK<I@KLKB@DLBJ<JJ8 KLKB@KK@@E G@KBWWE ?F@;FCC8 FCC<<E
@?FB<C@8B@8GFK@C88E A8 ?F@;<KLE B<C@8B@8M<IIFB@E J8@I88C8?F@KF@J@8 DLIKLD@8
!I@KP@J<JK@ KLKB@DLBJ<JJ8 B<JB@KPKK@@E CFEBB8DLIKLD@@E AF@;<E @CD88EKLMLLKK8 M<II8KK@@EDP_JCFEBB8DLIKLD8@CD88EKLMLLK<<E/LFD<EMW<JK_JJW+J8KP_
M@
@E<@JKFKFJ8K_@?@EA8B<IWKK@@EKLKB@DLBJ@8M8IK<EJLLEE@K<CCL@CC8BPJ<CP@CCWA8 FJ8KP_?_E ?88JK8KK<CLCC8 !CWDWEC88KL8 8IM@F@K@@E ,JP:?FCF>@:8C #<E<I8C 3<CC 9<@E>,#3–+J8KP_KA8/?FIK=IFD–BPJ<CP@;<E+J8KP_8MLCC8A8 M8KJ8F@I<@;<E M8@B<LKK8 8IM@F@K@@E #8JKIF@EK<JK@E8C /PDGKFDJ .8K@E> /:8C< – BPJ<CPCFD8BB<<CC8 +J8KP_K A8 0<IM<P;<E A8 ?PM@EMF@EE@E C8@KFBJ<E PCCWG@KWDWW?F@KF@CDF@KLJI<B@JK<I@WBWPK<KK@@EFJ8KP_JJW
%?FB<C@8B@8GFK@C88K BFB@M8K ;@8>EFFJ@M8@?<<JJ8 K<IM<PK<EJW ?<@B<EKPE<<BJ@ A8 ?<
BWIJ@MWK 8C<EKLE<<JK8 <CWDWEC88;LJK8 BFEKIFCC<@?@E M<II8KKLE8 *@@CCW
@?FB<C@8B@8GFK@C8@CC8 AFKB8BWIJ@MWK@?FF@I<@;<EC@JWBJ@M8KJ8F@I<@JK8 <CWDWEC88KLFC@
D8K8C8DG@BL@EE@@CCW AF@CC8M8KJ8F@I<@K8<@FCCLK,#3P?K<@JJLDD8 D<;@88E@
MJ 2LF;<EBLCLKKL8>CLK<<E@KKFD8EILFB8M8C@F?F@;FE8CF@KLBJ<JK8
<CWDWEC88KL FC@ J<BW M8KJ8F@I<@J@CC8 <KKW–F@I<<KKFD@CC8 @?FB<C@8B@8GFK@C8@CC8 J8D8CC8 K8JFCC8 BL@E K<IM<@CCW M<IIFB<@CC8 )P_J G@KBWWE ILFB8M8C@FCC8 FCC<@;<E
@?FB<C@8B@8GFK@C8@;<E <CWDWEC88KL FC@ M<IIFBB@<E K8JFCC8 ,#3 P?K<@JJLDD8 D<;@88E@ MJ <@BW ?F@;<KL@CC8 @?FB<C@8B@8GFK@C8@CC8 KF;<KKL G@KB@KKPE<@KW M8KJ8F@I<@K8 %KJ<@CDF@K<KKL <C@E@BW@E<E CLLEDLIKLD8I@JB@ KF;<KK@@E J8D8EB8CK8@J<BJ@ @?FB<C@8B@8JJ8 A8 B<C@8B@8JJ8 DLKK8 B<C@8B@8 K8@
@?FB<C@8B@8;@8>EFFJ@E AWCB<<E @?FB<C@8B@88 J8@I8JK8M@CC8 E8@J@CC8 KF;<KK@@E B<C@8B@88 J8@I8JK8M@@EE8@J@@EM<II8KKLE8D8K8C8DG@DLIKLD8I@JB@I@JB@K@?<PJJL?;< $.
CLFKK8DLJMWC@%–%?FB<C@8B@8GFK@C88K AFKB8I8GFIKF@M8KDLIKLD8E BWIJ@MWK ?8EB8C8DD@JK8 I<=CLBJ@F@I<@JK8 A8 BWPKK@MWK <E<DDWE GIFKFE@GLDGLE
<JKWAWCWWBB<@KW BL@E E< AF@CC8 <@ FCCLK DLIKLD88 )P_J J8@I88C8?F@KF@JK<E CLLEDLIKLD@<E I@JB@ ;@8>EFFJ@E AWCB<<E FC@ G@<E<DG@ @?FB<C@8B@8GFK@C8@CC8 BL@E B<C@8B@8M<IIFB<@CC8$. %–0WJKW?LFC@D8KK8J<BWB<C@8B@8JJ8
<KKW@?FB<C@8B@8JJ8CFEBB8DLIKLD8@CD88EKLMLL;<KFC@M8K/LFD<EMW<JK_EK8JFCC8 0WDW KLKB@DLJ FJF@KK@ <KKW @?FB<C@8B@88E C@@KKPP BF?FEELK K8LK@K88BB8
;@8>EFFJ@M8@?<<JJ8 A8 C@JWWEKPEPKKW K8LK@K88BB88 K8M8K88E <K<EB@E E@@CCW
@?FB<C@8B@8GFK@C8@CC8 AFKB8BWIJ@MWKM8KJ8F@I<@JK8(P?PKK8@G@KBW8@B8@J<JK@?F@;<KLJJ8
@?FB<C@8B@8JJ8 <CWDWEC88;LE <@ KF;<KKL 8C<EKLE<<E <@BW ?F@;<KKLLE @?FB<C@8B@88E C@@KKPEPK G@KB@KKPE<@KW M8KJ8F@I<@K8 @8>EFFJ@E AWCB<@E<E DLIKLD8I@JB@ KF;<KK@@E
@?FB<C@8B@8JJ8 B<C@8B@88 G@<E<DDWBJ@ (FEBB8DLIKLD8I@JB@ <@ FCCLK MW<JK__E M<II8KKLE8C@JWWEKPEPK@?FB<C@8B@8JJ8 DLKK8<@DP_JBWWEB<C@8B@8JJ8 AF?FE8@<DG@<E KLKB@DLJK<EG<ILJK<<CC8C@@KKPPC@JWWEKPEPKCFEBB8DLIKLD8I@JB@
M@@
+#&&%+%+*
/0.0@@@
0%%2%/0!()RM
.!2%0%+*/
(%/0+"+.%#%*(,1(%0%+*/
%*0.+ 10%+*
.!2%!3+"0$!(%0!.01.!
@J<8J<JG<:KILDF=:F<C@8:;@J<8J<
F<C@8:;@J<8J<
<ID8K@K@J?<IG<K@=FID@J
+K?<I<OKI8@EK<JK@E8CJPDGKFDJF=:F<C@8:;@J<8J<
.@JB>IFLGJ8E;8JJF:@8K<;:FE;@K@FEJ
,8K?F><E<J@J
#<E<K@:J
#CLK<E8E;<EM@IFED<EK
/D8CC9FN<CG8K?F><E<J@J
/B@E@DDLEFG8K?F><E<J@J@E;<ID8K@K@J?<IG<K@=FID@J
!G@;<D@FCF>P
@8>EFJ@J
/D8CC9FN<C9@FGJ@<J
/B@E9@FGJ@<J
/<IFCF>P
0I<8KD<EK
#CLK<E=I<<;@<K
YLLL
8GJFE<D<;@:8K@FE@E;<ID8K@K@J?<IG<K@=FID@J
"FCCFNLG
(FE>K<IDGIF>EFJ@J
*<NKI<8KD<EKJ
FE<D@E<I8C;<EJ@KP8E;=I8:KLI<J
FE<D@E<I8C;<EJ@KP@E:F<C@8:;@J<8J<
FE<=I8:KLI<J@E:F<C@8:;@J<8J<
FE<8E;;<ID8K@K@J?<IG<K@=FID@J
@J<8J<.<C8K<;9LI;<E
-L8C@KPF=C@=<
$<8CK?I<C8K<;HL8C@KPF=C@=<@E:F<C@8:;@J<8J<
$<8CK?I<C8K<;HL8C@KPF=C@=<@E;<ID8K@K@J?<IG<K@=FID@J $<8CK?I<C8K<;HL8C@KPF=C@=<@EFK?<I:?IFE@:JB@E;@J<8J<J
!:FEFD@:9LI;<E
LI;<EF=>CLK<E=I<<;@<K
0$!,.!/!*0/01 5
@DJ
/KL;PG8K@<EKJ8E;:FEKIFCJ
<ID8K@K@J?<IG<K@=FID@JJKL;PG8K@<EKJ–
F<C@8:;@J<8J<:FEKIFCJ–
$<8CK?P:FEKIFCJ
)<K?F;J
)<;@:8CHL<JK@FEE8@I<J
)<;@:8C@EK<IM@<N
-L8C@KPF=C@=<8E;>8JKIF@EK<JK@E8CJPDGKFDJ–
FE<=I8:KLI<J–
/K8K@JK@:8C8E8CPJ<J–
!K?@:8C:FEJ@;<I8K@FEJ–
.<JLCKJ
,8K@<EKJ8E;;<DF>I8G?@:;8K8–
Patients’ selfG<I:<@M<;<OG<I@<E:<J 1J<F=D<;@:8K@FE8E;?<8CK?:8I<I<JFLI:<J
$<8CK?I<C8K<;HL8C@KPF=C@=<–
#8JKIF@EK<JK@E8C8E;<OKI8@EK<JK@E8CJPDGKFDJ–
FE<=I8:KLI<J–
@J:LJJ@FE
-L8C@KPF=C@=<
1J<F=?<8CK?:8I<I<JFLI:<J8E;D<;@:8K@FE
FE<=I8:KLI<J
/KI<E>K?J8E;C@D@K8K@FEJF=K?<JKL;P
/LDD8IP8E;:FE:CLJ@FEJ
C@E@:8C@DGC@:8K@FEJ8E;=LKLI<GIFJG<:KJ
'*+3(! #!)!*0/
.!"!.!*!/
,,!* %4/01 5-1!/0%+**%.! /!(%*!
,,!* %4/01 5-1!/0%+**%.! "+((+31,
,,!* %4 %/!/!.!(0! -1!/0%+**%.! $
,,!* %4 %/!/!.!(0! -1!/0%+**%.! +!(%
%/!/!
+.%#%*(,1(%0%+*/
LO
[
)- + &%*
) 9FE<D@E<I8C;<EJ@KP
)% 9F;PD8JJ@E;<O
-F( F<C@8: @J<8J<-L8C@KPF=(@=</LIM<P - F<C@8:;@J<8J<HL<JK@FEE8@I<
% :FE=@;<E:<@EK<IM8C
(5 ;@J89@C@KP8;ALJK<;C@=<P<8IJ $ ;<ID8K@K@J?<IG<K@=FID@J #, ;<8D@E8K<;>C@8;@EG<GK@;<
.- ;@J<8J<I<C8K<;HL<JK@FEE8@I<
4 ;L8C<E<I>P4I8P89JFIGK@FD<KIP
!D <E;FDPJ@8C8EK@9F;P
#/./ #8JKIF@EK<JK@E8C/PDGKFDJ.8K@E>/:8C<
$( ?LD8EC<LBF:PK<8EK@><E
$. ?8Q8I;I8K@F
$.-F( ?<8CK?I<C8K<;HL8C@KPF=C@=<
% %EK<IE8K@FE8C/K8K@JK@:8CC8JJ@=@:8K@FEF= @J<8J<J
%> @DDLEF>CF9LC@E
%( @EK<IC<LB@E
%-. @EK<IHL8IK@C<I8E><
)$ D8AFI?@JKF:FDG8K@9@C@KP:FDGC<O
*$ . *8K@FE8C$FJG@K8C @J:?8I><.<>@JK<I
*$( EFEHodgkin’s lymphoma
0# KI8EJ>CLK8D@E8J<
+. F;;JI8K@F
,#3 ,JP:?FCF>@:8C#<E<I8C3<CC<@E>
,,% GIFKFEGLDG@E?@9@KFI
,.+) G8K@<EKI<GFIK<;FLK:FD<D<8JLI<
. I<=I8:KFIP:F<C@8:;@J<8J<
/" /?FIK"FID
//.% J<C<:K@M<J<IFKFE@EI<:<GKFI@E?@9@KFIJ 3$+ 3FIC;$<8CK?+I>8E@Q8K@FE
# *+&&) %#',# + &%*
0?@JK?<J@J@J98J<;FEK?<=FCCFN@E>FI@>@E8CGL9C@:8K@FEJ N?@:?8I<I<=<II<;KF@E K?<K<OK9P.FD8EELD<I8CJ
,8JK<IE8:B '8LB@E<E ' 'LIGG8 ' )WB@ ) FCC@E , $<IMFE<E ' .<LE8C8 0 $L?K8C8 $ '<BBFE<E ( /8CD@ 0 #8JKIF@EK<JK@E8C /PDGKFDJ%E:I<8J<K?<LI;<EF=%CCE<JJ@E <ID8K@K@J$<IG<K@=FID@J ,IFJG<:K@M</KL;P:K8 <ID2<E<I<FC–
,8JK<IE8:B '8LB@E<E' 'LIGG8' )WB@) FCC@E, .<LE8C80 $L?K8C8
$ /8CD@0-L8C@KPF=(@=<8E;#8JKIF@EK<JK@E8C/PDGKFDJ@E(FE>
0<ID0I<8K<; <ID8K@K@J$<IG<K@=FID@J,8K@<EKJIFJJ/<:K@FE8C/KL;P
@E"@EC8E;D&C@E <ID8KFC–
,8JK<IE8:B )8EJ@BB8! '8LB@E<E' $<IMFE<E' .<LE8C80 FCC@E,
$L?K8C8 $ )8KK@C8 2) /8CD@ 0 /<C=I<GFIK<; =I8:KLI<J @E
;<ID8K@K@J?<IG<K@=FID@J:FDG8I<;KF:F<C@8:;@J<8J<*LKI@<EKJ
,8JK<IE8:B 'FJB@E<E% $<IMFE<E' '8LB@E<E' &WIM<C@E& .<LE8C80 FCC@E, $L?K8C8$ )8KK@C82) /8CD@0.@JBF==I8:KLI<J@E;<ID8K@K@J
?<IG<K@=FID@J8E;:F<C@8:;@J<8J<8I<>@JK<I98J<;JKL;P/L9D@KK<;
0?< FI@>@E8C GL9C@:8K@FEJ 8I< I<GL9C@J?<; N@K? K?< G<ID@JJ@FE F= K?< :FGPI@>?K
?FC;<IJ
%+)&,+ &%
F<C@8:;@J<8J<@J8>CLK<EJ<EJ@K@M<JD8CC9FN<C<EK<IFG8K?PN@K?8GI<M8C<E:<F=–
/@E>? <K 8C F<C@8: ;@J<8J< @J :?8I8:K<I@Q<; 9P 8 N@;< I8E>< F=
>8JKIF@EK<JK@E8C8E;<OKI8@EK<JK@E8CJPDGKFDJ8E;;L<KFK?<N@;<:C@E@:8CJG<:KILD 8E;8KK@D<JD@C;8E;M8>L<JPDGKFDJ :F<C@8:;@J<8J<@J8ELE;<I;@8>EFJ<;;@J<8J<
N@K?8CFE>;@8>EFJK@:;<C8P8@8E;@8::@+E:<;@8>EFJ<; >CLK<E=I<<;@<K
@JK?<:FIE<IJKFE<F=KI<8KD<EK@E:F<C@8:;@J<8J<0?<JKI@:KC@=<CFE>;@<K ?FN<M<I
@JJF:@8CCPI<JKI@:K@M< K@D<:FEJLD@E>8E;;@==@:LCKKF:FDGCPN@K?/<<<K8C ,IFCFE><;>CLK<E:FEJLDGK@FE;L<KF;@8>EFJK@:;<C8P8E;GFFI8;?<I<E:<KF;@<K GI<;@JGFJ<J:F<C@8:;@J<8J<G8K@<EKJKF@E:I<8J<;I@JBF=:FDGC@:8K@FEJ8E;FE<F=K?<
DFJK:FDDFE:FDGC@:8K@FEI<C8K<;KF:F<C@8:;@J<8J<@JK?<9FE<=I8:KLI<JFE<
=I8:KLI<I@JB?8J9<<EJ?FNEKF9<<C<M8K<;@E:F<C@8:;@J<8J<8E;@JD8@ECPK?FL>?K KF9<8JJF:@8K<;N@K?JD8CC9FN<CDL:FJ8CM@CCFLJ;8D8><8==<:K@E>K?<89JFIGK@FE F=ELKI@<EKJ$<@BB@CW<K8C
L<KF;@==@:LCK8E;;@M<IJ<JPDGKFDJ :?8CC<E>@E>KI<8KD<EK8E;KIFL9C<JFD<
:FDGC@:8K@FEJ 8E @E:I<8J<; 9LI;<E F= ;@J<8J< ?8J 9<<E J?FNE KF 9< I<C8K<; KF :F<C@8:;@J<8J<0?<9LI;<E@JDFJKGI<M8C<EK@ELEKI<8K<;:F<C@8:;@J<8J<LEKI<8K<;
:F<C@8:;@J<8J<G8K@<EKJG<I:<@M<K?<@IHL8C@KPF=C@=<@DG8@I<;8E;LJ<DFI<?<8CK?
:8I<I<JFLI:<J8E;D<;@:8K@FEJ:FDG8I<;KF:FEKIFCJ*8:?D8E<K8C1BBFC8
<K8C8 <JG@K<K?<D8EPE<>8K@M<8JG<:KJF=>CLK<E=I<<;@<K K?<9LI;<E@E :F<C@8:;@J<8J<;<:I<8J<J8=K<IK?<@E@K@8K@FEF=K?<KI<8KD<EK1BBFC8<K8C9 LI><I<K8C*<M<IK?<C<JJ HL8C@KPF=C@=<;F<JEFKEFID8C@Q<N@K?K?<>CLK<E
=I<<;@<K8E;K?<LJ<F=?<8CK?:8I<I<JFLI:<JI<D8@EJ@E:I<8J<;:FDG8I<;KFK?<
><E<I8CGFGLC8K@FE2@FC8KF<K8CLI><I<K8C%E8;;@K@FE K?<9LI;<E
;F<JEFKFECP:FE:<IE:F<C@8:;@J<8J<G8K@<EKJ9LK8CJFK?<@IEFE:F<C@8:G8IKE<IJ .FP<K8C9
<ID8K@K@J ?<IG<K@=FID@J $ @J 8 N<CC:?8I8:K<I@Q<; <OKI8@EK<JK@E8C D8E@=<JK8K@FEF=:F<C@8:;@J<8J<%EG8K@<EKJN@K? $ >CLK<E@E;L:<J8E@EK<EJ@M<CP
@K:?@E>9C@JK<I@E>I8J?8E;@E8;;@K@FEK?<:F<C@8:KPG<JD8CC9FN<CDL:FJ8C8KIFG?P 8E;@E=C8DD8K@FE $@J8CJFKI<8K<;N@K?JKI@:K>CLK<E=I<<;@<K8E;K?<;@<K?<8CJ 9FK?K?<DL:FJ8CM@CCFLJ8KIFG?P8E;K?<I8J?.<LE8C8 <JG@K< $9<@E>8 :LK8E<FLJD8E@=<JK8K@FEF=:F<C@8:;@J<8J<KI<8K<;N@K?K?<J8D<I<JKI@:K@M<>CLK<E
=I<<;@<K 8E;@E8;;@K@FE8:?IFE@:@K:?@E>JB@E;@J<8J< K?<9LI;<E8E;HL8C@KPF=C@=<
@E $?8M<JF=8I9<<EI8I<CPJKL;@<;CJF M<IPC@KKC<@JBEFNE89FLKK?<9FE<
=I8:KLI< I@JB @E $ 8CK?FL>? $ G8K@<EKJ ?8M< K?< J8D< JD8CC 9FN<C DL:FJ8C M@CCFLJ8KIFG?P8J:F<C@8:;@J<8J<G8K@<EKJ 8CK?FL>?K?@J@JLJL8CCPC<JJJ<M<I<
0?<8@DF=K?<;@JJ<IK8K@FEN8JKF<JK@D8K<K?<9LI;<EI<C8K<;KF9FK?LEKI<8K<;
8E; KI<8K<; $ 9P JKL;P@E> HL8C@KP F= C@=< LJ< F= ?<8K? :8I< I<JFLI:<J 8E;
D<;@:8K@FE8E;K?<=I8:KLI<I@JB@E $G8K@<EKJ
)- .&+# +)+,)
***'+),$&&# **
A7>;356;E73E7
F<C@8: ;@J<8J< @J 8 :?IFE@: 8LKF@DDLE<D<;@8K<; JD8CC 9FN<C <EK<IFG8K?P %E :F<C@8:;@J<8J<@E><JK<;>CLK<EG<GK@;<JKI@>><I8JD8CC9FN<CDL:FJ8C@E=C8DD8K@FE 8E; M@CCFLJ 8KIFG?P @E ><E<K@:8CCP JLJ:<GK@9C< @E;@M@;L8CJ 1EK@C K?< J :F<C@8:
;@J<8J<N8J:FEJ@;<I<;8I8I<<EK@KPF::LII@E>D8@ECP@E:?@C;I<E8J8D8C89JFIGK@FE
;@JFI;<I N@K? FM<IK >8JKIF@EK<JK@E8C JPDGKFDJ 8E; N<@>?K CFJJ /@E:< K?<E K?<
GI<M8C<E:<F=K?<;@J<8J<?8J@E:I<8J<;/@E>?<K8C8E;@KJ:C@E@:8CGI<J<EK8K@FE
?8J9<:FD<DFI<;@M<IJ<FKK8IF<K8C'@M<CW<K8C
%E 8CC :F<C@8: ;@J<8J< G8K@<EKJ K?< >CLK<E;<G<E;<EK @DDLE< I<8:K@FE 8==<:KJ GI@D8I@CPK?<JD8CC@EK<JK@E<0?<I<=FI<>8JKIF@EK<JK@E8CJPDGKFDJJL:?8J9CF8K@E>
CFFJ< JKFFCJ 8E; 89;FD@E8C G8@E FI ;@J:FD=FIK 8I< JK@CC 8 :FDDFE EL@J8E:< =FI G8K@<EKJN@K?:F<C@8:;@J<8J<$FN<M<I :F<C@8:;@J<8J<8==<:KJD8EP;@==<I<EKFI>8EJ 8E; K?LJ 8 N@;< I8E>< F= <OKI8@EK<JK@E8C JPDGKFDJ ?8M< 9<:FD< @E:I<8J@E>CP :FDDFE2FCK8<K8C'@M<CW<K8C0?<J<<OKI8@EK<JK@E8CJPDGKFDJ8I<
;@J:LJJ<;@E;<K8@C@E?8GK<IJ8E;%E8;;@K@FE KFK8CCP8JPDGKFD8K@::F<C@8:
;@J<8J<<O@JKJ8E;@JKPG@:8CCP;<K<:K<;@EG8K@<EKJ9<CFE>@E>KF:F<C@8:;@J<8J<8KI@JB
>IFLGJ JL:? 8J I<C8K@M<J F= :F<C@8: ;@J<8J< G8K@<EKJ FI @E G8K@<EKJ N@K? FK?<I 8LKF@DDLE<;@J<8J<J?8GK<I8E;089C<"8J8EF<K8C
7D?3F;F;E:7DB7F;8AD?;E
<ID8K@K@J?<IG<K@=FID@J $N8J=@IJK;<J:I@9<;9P(FL@J L?I@E>@E8J8 C@=<CFE>M@FC<EKCP@K:?@E>JB@E;@J<8J< L?I@E> @==<I<EK@8C;@8>EFJK@:J=IFD FK?<I 9C@JK<I@E> 8LKF@DDLE< JB@E ;@J<8J<J 9<:8D< GFJJ@9C< @E N?<E JB@E
@DDLEF=CLFI<J:<E:<=@E;@E>JKPG@:8C=FI $N<I<;<J:I@9<;28E <I)<<I
%EK?<J@KN8J=LIK?<IF9J<IM<;K?8KK?<D8AFI@KPF= $G8K@<EKJ?8;>CLK<E I<8:K@M< JD8CC9FN<C DL:FJ8C M@CCFLJ 8KIFG?P )8IBJ <K 8C 3<@EJK<@E <K 8C 8E;:LII<EKCP $@JN@;<CP8::<GK<;8J8:LK8E<FLJD8E@=<JK8K@FEF=:F<C@8:
;@J<8J<.<LE8C8FCC@E<K8C
0?< KPG@:8C GI<J<EK8K@FE F= $ @J 8E @EK<EJ< GILI@KLJ N@K? 8 JPDD<KI@:
GFCPDFIG?@:9C@JK<I@E>I8J?.<LE8C80?<DFJK:FDDFEJ@K<JF=K?<I8J?8I<
K?<<OK<EJFIJLI=8:<JF=K?<<C9FNJ8E;BE<<J 9LKKF:BJ 98:B8E;J:8CG0?<I8J?
D8P8CJF8GG<8IFEK?<89;FD<E >IF@EFI=8:<<M<EFI8CC<J@FEJ?8M<9<<EI<GFIK<;
9LKK?<J<8I<I8I<(W?K<<EFA8<K8C0?< $9C@JK<IJ8I<I<C8K@M<CPJD8CC8E;
8I<=I<HL<EKCP<IF;<;8E;:ILJK<;8J8I<JLCKF=J:I8K:?@E>.<LE8C8 $@J F=K<EJLJG<:K<;@EK?<GI<J<E:<F=GILI@KLJ8E;I8J?8KKPG@:8C $CF:8K@FEJ9LK@K :8E 8CJF 9< :FE=FLE;<; N@K? FK?<I @K:?@E> JB@E ;@J<8J<J .<LE8C8 0?<
GI<J<E:<F=>8JKIF@EK<JK@E8CJPDGKFDJ@E $?8J9<<EC@KKC<JKL;@<;9LKK?<:C@E@:8C :FEJ<EJLJ@JK?8KK?<>8JKIF@EK<JK@E8CJPDGKFDJK?8KD8P8GG<8I@E8JJF:@8K@FEN@K?
$8I<F=K<ED@EFIFCC@E<K8C
CK?FL>? K?<I< @J EF ;FL9K K?8K $ 9<CFE>J KF K?< :F<C@8: ;@J<8J< JG<:KILD FCC@E <K 8C @E K?@J K?<J@J K?< K<ID :F<C@8: ;@J<8J< @J LJ<; KF I<=<I KF 8CC G?<EFKPG<JF=:F<C@8:;@J<8J<FK?<IK?8E $
&F:7D7JFD3;@F7EF;@3>EK?BFA?EA85A7>;356;E73E7
%E8;;@K@FEKF $ 8M8I@<KPF=FK?<I<OKI8@EK<JK@E8CJPDGKFDJF=:F<C@8:;@J<8J<8I<
BEFNE%E:?@C;?FF;:F<C@8:;@J<8J<K?<DFJK=I<HL<EK<OKI8@EK<JK@E8CD8E@=<JK8K@FE
@JGFFI>IFNK?8E;K?@J@J8JJF:@8K<;N@K?DFI<J<M<I<;@J<8J<*LID@E<E<K8C <C8P<;GL9<IKP8E;<E8D<C;<=<:KJD8PF::LI@E:?@C;I<EN@K?:F<C@8:;@J<8J<@E<
FKK8IF<K8C 8E;8JK?<<E8D<C;<=<:KJ8I<G<ID8E<EKK?<P8CJFG<IJ@JK KF8;LCK?FF;@E<<K8CE8<D@8D8PF::LI@E8CC8><>IFLGJ @JFE<F=K?<
DFJK:FDDFE<OKI8@EK<JK@E8CGI<J<EK8K@FEF=:F<C@8:;@J<8J<8E;@J8CJFC@EB<;KF DFI< J<M<I< ;@J<8J< 9L 8P8 <K 8C /8LBBFE<E <K 8C E8<D@8 @E :F<C@8:;@J<8J<@J:8LJ<;9PD8C89JFIGK@FEF=D@:IFELKI@<EKJJL:?8J@IFE 8E;DFI<
I8I<CP=FC@:8:@;FIM@K8D@E 9LKK?<:?IFE@:@E=C8DD8K@FED8P8CJF:FEKI@9LK<
<I>8D8J:?@<K8C0?<C@M<I<EQPD<J8I<<C<M8K<;@ELGKFF=E<NCP
;@8>EFJ<;G8K@<EKJ8E;K?<J<ILDKI8EJ8D@E8J<JF=K<EEFID8C@Q<N@K?>CLK<E=I<<
;@<K/8@EJ9LIP<K8C%E8;;@K@FE :F<C@8:;@J<8J<I<C8K<;E<LIFCF>@:JPDGKFDJ
?8M< 9<<E J?FNE KF F::LI K?< DFJK :FDDFE F= K?<J< 9<@E> >CLK<E 8K8O@8 8E;
G<I@G?<I8CE<LIFG8K?P$8;A@M8JJ@C@FL<K8CI@8E@<K8C0?8N8E@<K8C &F@EK JPDGKFDJ @E:CL;@E> G8@E 8E; JN<CC@E> ?8M< 8CJF 9<<E I<GFIK<;
(L9I8EF <K 8C "LIK?<IDFI< :F<C@8: ;@J<8J< @J C@EB<; KF GIF9C<DJ N@K?
I<GIF;L:K@FE/@E>?<K8CFE<D@E<I8C;<EJ@KP) @JF=K<E;<:I<8J<;@E LEKI<8K<;:F<C@8:;@J<8J<8E;@J;@J:LJJ<;@E>I<8K<I;<K8@C@E?8GK<I
);E=9DAGBE3@63EEA5;3F765A@6;F;A@E
0?<I<C8K@M<JF=:F<C@8:;@J<8J<8E; $G8K@<EKJ8I<8K@E:I<8J<;I@JBF=?8M@E>9FK?
;@JFI;<IJ .<LE8C8 ::FI;@E> KF 8 I<:<EK D<K88E8CPJ@J K?< GI<M8C<E:< F=
:F<C@8:;@J<8J<FI $@E=@IJK;<>I<<I<C8K@M<JF=@E;@M@;L8CJN@K?<@K?<ID8E@=<JK8K@FE
@J J@9C@E>J9<@E>K?<DFJKF=K<E8==<:K<;$<IMFE<E<K8C/@E>?<K8C
F<C@8: ;@J<8J< @J 8JJF:@8K<; N@K? :<IK8@E ><E<K@: ;@JFI;<IJ %E;@M@;L8CJ N@K?
Down’s syndrome are at 6=FC; I@JB F= :F<C@8: ;@J<8J< 8E; K?FJ<with Turner’s JPE;IFD< 8I< 8K =FC; I@JB =FI :F<C@8: ;@J<8J< :FDG8I<; KF ><E<I8C GFGLC8K@FE )XI@C;<K8C CJF K?<GI<M8C<E:<F=%>;<=@:@<E:P@J@E:F<C@8:
;@J<8J<G8K@<EKJ8E;K?LJ?@>?<IK?8E@E><E<I8CGFGLC8K@FE?FN<K8C ,8CC8M<K8C,8IK@8C%>;<=@:@<E:P?8J8CJF9<<EI<GFIK<;@E $ 9LK8::FI;@E>
KF:LII<EKBEFNC<;><KFK8C%>;<=@:@<E:P:8EEFK<D<I><@E $8JK?<GI<J<E:<F=
%>@JK?<G8K?F>EFDFE@:=@E;@E>@E $/8DFC@K@J<K8C
)8EP 8LKF@DDLE< :FE;@K@FEJ 8I< BEFNE KF F::LI @E 8JJF:@8K@FE N@K? :F<C@8:
;@J<8J< 8E; $ %E 8 C8I>< JKL;P =IFD <ED8IB 8LKF@DDLE< :FDFI9@;@K@<J F::LII<;@EF=:F<C@8:;@J<8J<G8K@<EKJ8E;F=><E<I8CGFGLC8K@FE#IF;<
<K8CFDDFE8JJF:@8K<;8LKF@DDLE<;@J<8J<J8I<KPG<;@89<K<JD<CC@KLJ 8LKF@DDLE< K?PIF@; ;@J<8J< Sjögren’s syndrome and 8LKF@DDLE< C@M<I ;@J<8J<
089C<"LIK?<IDFI< 8GGIFO@D8K<CPF=G8K@<EKJN@K?KPG<;@89<K<J?8M<9<<E
;@8>EFJ<;N@K?:F<C@8:;@J<8J<!C=JKI_D<K8C 8E;8DFE>8;LCKG8K@<EKJN@K?
8LKF@DDLE< K?PIF@; ;@J<8J< K?< GI<M8C<E:< F= 9@FGJPGIFM<E :F<C@8: ;@J<8J< ?8J 9<<E .FP <K 8C 8In patients with Sjögren’s syndroDe or Addison’s
;@J<8J< :F<C@8:;@J<8J<?8J9<<E=FLE;@E8E;F=@E;@M@;L8CJI<JG<:K@M<CP
%CK8E<E<K8C)P?I<<K8C.<:<EKCP 8:FEE<:K@FE9<KN<<E $ 8E;KF 8 C<JJ<I <OK<EK :F<C@8: ;@J<8J< N@K? 8EFK?<I 8LKF@DDLE< 9LCCFLJ ;@J<8J< 9LCCFLJ G<DG?@>F@; N8J I<GFIK<; @E 8 C8I>< :8J<:FEKIFC JKL;P 28IGLCLFD8 <K 8C
"LIK?<I FK?<I8LKF@DDLE<JB@E;@J<8J<J?8M<9<<EJ?FNEKFJGFI8;@:8CCP:FF::LI N@K?:F<C@8:;@J<8J<8E; $.F;I@>F<K8C .<LE8C88E;FCC@E
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jögren’s syndrome ;44P7F3>"D;E:@3D766K7F3>@39@AEFABAG>AE7F3> "D;E:@3D766K7F3>&:3F37F3>;D>;=7F3> )7G@3>33@6A>>;@)7G@3>33@6A>>;@3G97@7F3> +*&"$$+%!'*"*") ;44P7F3>"D;E:@3D766K7F3>";?7F3> "D;E:@3D766K7F3>DT@437=7F3> Addison’s disease "D;E:@3D766K7F3>"D;E:@3D766K7F3>&>38EEA@3@6*;9GD<A@E6AFF;D >8EFDQ?7F3>)7G@3>33@6A>>;@$7K7D7F3> )7G@3>33@6A>>;@ "*"#" & ;44P7F3>3@637F3>1:3@97F3> "D;E:@3D766K7F3>"D;E:@3D766K7F3> %ADEFDQ?7F3> #&'" "D;E:@3D766K7F3>3@637F3>*383H; %ADEFDQ?7F3>"D;E:@3D766K7F3> )7G@3>33@6A>>;@)7G@3>33@6A>>;@
'+&%* *
7@7F;5E
F<C@8:;@J<8J<8E; $8I<GFCP><E<K@:;@J<8J<J8E;K?<><E<K@:GI<;@JGFJ@K@FE@J
<JJ<EK@8C=FI;@J<8J<;<M<CFGD<EK 8CK?FL>?>CLK<E@JK?<KI@>><IF=K?<;@J<8J</FCC@;
8E;&89I@0?<DFJK@DGFIK8EK><E<K@:=8:KFI9<?@E;:F<C@8:;@J<8J<8E; $
@JK?<><E<:CLJK<IF=:?IFDFJFD<J@O:8CC<;K?<D8AFI?@JKF:FDG8K@9@C@KP:FDGC<O )$%%'8KQ<K8C/KFB<J<K8C0?<)$%%<E:F;<J:<CCJLI=8:<
GIFK<@EJ :8CC<; ?LD8E C<LBF:PK< 8EK@><EJ $( 0?<J< D<D9I8E<9FLE;
>CP:FGIFK<@EJ8I<=FLE;@E8EK@><EGI<J<EK@E>:<CCJ8E;K?<@I=LE:K@FE@JKFGI<J<EK G<GK@;<JKF@DDLE<:<CCJ/FCC@;8E;&89I@
0?<$(DFC<:LC<J8I<?<K<IF;@D<IJ:FEJ@JK@E>F=ơand Ƣ:?8@EJ<E:F;<;9P
$( -8E;$( -><E<J0?<$( -?8GCFKPG<@JGI<J<EK@EDFI<
K?8E F= :F<C@8: ;@J<8J< 8E; $ G8K@<EKJ 8E; @J <E:F;<; 9P K?<
$( - 8E; $( - 8CJF :8CC<; $( - 8CC<C<J ,I8:K@:8CCP 8CC K?< I<D8@E@E> G8K@<EKJ ?8M< K?< $( - ?8GCFKPG< <E:F;<; 9P 8CC<C<J$( -8E;$( -/FCC@;<K8C/GLIBC8E;<K8C '8I<CC <K 8C $( ;FJ8>< D8P 8==<:K K?< I@JB F= ;<M<CFG@E> :F<C@8:
;@J<8J<(@L<K8C 8E;8CK?FL>?$( -?FDFQP>FJ@J?8J9<<E8JJF:@8K<;
N@K?DFI<J<M<I<:F<C@8:;@J<8J<'8I@E<E<K8C FK?<IJKL;@<J?8M<=8@C<;KF F9J<IM<8EP8JJF:@8K@FE9<KN<<EK?<$(I<>@FE8E;J<M<I@KPFID8E@=<JK8K@FEF=
:F<C@8:;@J<8J<&F?EJFE<K8C0?FD8J<K8C>8I;?<K8C0?<
D8KK<I@J=LIK?<I<DG?8J@Q<;@E8KN@EJKL;PI<GFIK@E>DFEFQP>FK@:KN@EJN@K?FE<
?8M@E>:F<C@8:;@J<8J<8E;K?<FK?<I $$<IMFE<E<K8C$FN<M<I N?@C<K?<
$( -8E; -?8GCFKPG<J<O@JK@ELGKFF=EFIK?<IEGFGLC8K@FE'XI?LJ
<K8C8 K?<P8I<E<:<JJ8IP9LKEFKJL==@:@<EK=FIK?<G8K?F><E<J@J8E;K?LJK?<
D8AFI@KPF=:8II@<IJN@CCE<M<I;<M<CFG:F<C@8:;@J<8J<FI $%E8;;@K@FE FM<I EFE$(I<>@FEJ?8M<9<<E=FLE;KF@E:I<8J<K?<I@JBF=:F<C@8:;@J<8J<8E; $ 0IPEB8<K8C
>GF7@3@67@H;DA@?7@F
0?<GIFC8D@EJKFI8><GIFKeins in wheat, barley and rye are collectively called ‘gluten’.
)FI<JG<:@=@:8CCP K?<GIFK<@EJ@EN?<8K8I<:8CC<;I<JG<:K@M<CP>C@8;@EJ8E;>CLK<E@EJ 8E;@E98IC<P8E;IP<?FI;<@EJ8E;J<:8C@EJ/FCC@;8E;&89I@%E><JK<;>CLK<E
@J8GI<I<HL@J@K<=FIKI@>><I@E>:F<C@8:;@J<8J<8E; $$FN<M<I @K@JLE:C<8IN?P K?< ;@J<8J< GIF:<JJ @J KI@>><I<; @E FECP 8 JD8CC GFIK@FE F= ><E<K@:8CCP JLJ:<GK@9C<
@E;@M@;L8CJ0?<8DFLEKF=;@<K8IP>CLK<E:FEJLD<;J<<DJKF9<8JJF:@8K<;N@K?K?<
GI<M8C<E:<F=:F<C@8:;@J<8J<8K8E<G@;<D@FCF>@:8CC<M<C.8D8BI@J?E8<K8C /@E>?<K8C0?<K@D@E>F=>CLK<E@EKIF;L:K@FE@E:?@C;?FF;8CJF?8JJFD<
<==<:KJ8JC8K<>CLK<E@EKIF;L:K@FE@E:I<8J<JK?<;@8>EFJK@:8><(@FE<KK@<K8C 8E;8CJFJ<<DJKFJC@>?KCP@E:I<8J<K?<I@JBF=><E<I8K@E>:F<C@8:;@J<8J<IFEJJFE
<K8C,@EKF/UE:?<Q<K8C
0?<I<@J<M@;<E:<K?8KEFE;@<K8IPI@JB=8:KFIJ8I<8CJF@EMFCM<;@EKI@>><I@E>CFJJ F=>CLK<EKFC<I8E:<(@E;=FIJ<K8C%E=<:K@FEJ8E;EFID8C@EK<JK@E8CD@:IF9@FK8
;FNEI<>LC8K<@DDLE@KP8E;DF;LC8K<@DDLE<KFC<I8E:<"FIK?@JI<8JFEK?<?P>@<E<
?PGFK?<J@J?8J9<<EJL>><JK<;KF<OGC8@EK?<@E:I<8J<;@E:@;<E:<F=:F<C@8:;@J<8J<
8E; FK?<I 8LKF@DDLE< ;@J<8J<J @E K?< ;<M<CFG<; :FLEKI@<J 8:? M8JK
><F>I8G?@:8C>I8;@<EK@EK?<@E:@;<E:<F=:F<C@8:;@J<8J<9<KN<<E"@EC8E;8E;.LJJ@8 JLGGFIKJK?<?P>@<E<?PGFK?<J@J8JK?<><E<K@:GI<;@JGFJ@K@FE=FI:F<C@8:;@J<8J<8E;
K?<LJ<F=>I8@EJ@EK?<J<KNFGFGLC8K@FEJ@J=8@ICPJ@D@C8I9LKK?<JF:@F<:FEFD@:
<EM@IFED<EK;@==<IJ'FE;I8J?FM8<K8C%E8;;@K@FE D8EP=8:KFIJI<C8K<;KF K?< G<I@ FI GFJKE8K8C G<I@F; ?8M< 9<<E ;<K<:K<; JL:? 8J 9<@E> 9FIE ;LI@E> K?<
JLDD<I J<8JFE (<9NF?C <K 8C 08EGFNGFE> <K 8C FI 9P <C<:K@M<
:8<J8I<8EJ<:K@FE <:B<I<K8C)XI@C;<K8C?8M<9FK?9<<E8JJF:@8K<;
N@K? @E:I<8J<; I@JB F= :F<C@8: ;@J<8J< 0?< GIFK<:K@M< <==<:K F= 9I<8JK=<<;@E>
<OGC8@E<;9PK?<?@>?ELD9<IJF=@DDLEFDF;LC8K@E>8E;8EK@D@:IF9@8CDFC<:LC<J
@E9I<8JKD@CB?8J8CJF9<<EGIFGFJ<; 9LK8I<:<EKD<K88E8CPJ@J=8@C<;KFF9J<IM<
JL:? 8 J@>E@=@:8E:< ,@EKF/UE:?<Q <K 8C GFJ@K@M< 8JJF:@8K@FE 9<KN<<E
>8JKIF@EK<JK@E8C8E;FK?<IKPG<JF=@E=<:K@FEJ8E;;<M<CFGD<EKF=:F<C@8:;@J<8J<?8J 9<<EI<GFIK<;@ED8EPJKL;@<J/K<E<<K8C)XI@C;<K8C'<DGG8@E<E<K 8C'XI?LJ<K8C 8E;8CK<I<;;LF;<E8C8E;=8<:8CD@:IF9@FK8?8J8CJF 9<<EC@EB<;KF:F<C@8:;@J<8J<#@I9FM8E<K8C%E8;;@K@FE $G8K@<EKJ?8M<
9<<E J?FNE KF ?8M< ;@==<I<EK D@:IF9@FK8 N?<E :FDG8I<; N@K? :F<C@8: ;@J<8J<
G8K@<EKJN@K?>8JKIF@EK<JK@E8CJPDGKFDJ38:BC@E<K8C 9LKFK?<IK?8EK?8K M<IPC@KKC<@JBEFNE89FLKK?<><E<I8K@FEF=;@==<I<EKG?<EFKPG<JF=:F<C@8:;@J<8J<
*?3>>4AI7>B3F:A97@7E;E
0?<@E><JK<;>CLK<E@J@E:FDGC<K<CP;@><JK<;@EK?<?LD8E>8JKIF@EK<JK@E8CJPJK<D N?@:?C<8;JKFK?<><E<I8K@FEF=?8ID=LC>C@8;@EG<GK@;<J@EK?<JD8CC9FN<CCLD<E 0?<J<G<GK@;<J><E<I8K<8E@E=C8DD8KFIPI<8:K@FEM@8K?<@EE8K<@DDLE<JPJK<D@E K?<JD8CC9FN<CDL:FJ8/FCC@;8E;&89I@0?<KFO@:>C@8;@EG<GK@;<JJ<<DKF
?8M<;@M<IJ<?8ID=LC<==<:KJFEK?<DL:FJ8 9LKFE<F=K?<DFJK@DGFIK8EK@JK?<
GIF;L:K@FEF=@EK<IC<LB@E%(@EDL:FJ8C:<CCJ)8@LI@<K8C0?<%(8E;
FK?<I:F<O@JK@E>=8:KFIJ@E;L:<8JKI<JJI<8:K@FE@EK?<<G@K?<C@8C98II@<I :8LJ@E>K?<
C<8B8><F=>C@8;@E=I8>D<EKJ@EKFK?<C8D@E8GIFGI@8)<I<JJ<<K8C/<KKP<K8C
0?< <EQPD< :8CC<; K@JJL< KI8EJ>CLK8D@E8J< 0# ?8J 8 B<P IFC< @E K?<
G8K?F><E<J@JF=:F<C@8:;@J<8J<8J@K?8JK?<89@C@KPKF;<8D@E8K<>C@8;@EG<GK@;<J@E K?<C8D@E8GIFGI@80?@J;<8D@E8K@FE@E:I<8J<J>C@8;@EJ’8==@E@KPKF9@E;K?<G<GK@;<
9@E;@E> >IFFM< F= K?< $( -DFC<:LC< )FC9<I> <K 8C 0?< 8EK@><E GI<J<EK@E> :<CCJ N@K? K?< $( ->C@8;@E:FDGC<O<J @EK<I8:K N@K? >C@8;@E JG<:@=@:0:<CCJ<E?8E:@E>K?<@I8:K@M@KP8E;I<JLCK@E>@E8;8GK@M<@DDLE<8:K@M8K@FE FEJ<HL<EKCP?@>?C<M<CJF=GIF@E=C8DD8KFIP:PKFB@E<JJL:?8J@EK<I=<IFEƣ and IL 8I< GIF;L:<; /FCC@; 8E; &89I@ 0?< GIF;L:K@FE F= GIF@E=C8DD8KFIP :PKFB@E<J 8E; %( GIF;L:<; @E K?< DL:FJ8C :<CCJ ><E<I8K< 8E 8GGIFGI@8K<
<EM@IFED<EK =FI K?< ;@==<I<EK@8K@FE 8E; 8:K@M8K@FE F= @EKI8<G@K?<C@8C :PKFKFO@: 0 CPDG?F:PK<J 0?@J ;PJI<>LC8K<; 8:K@M8K@FE C<8;J KF K?< J<C<:K@M< ;<JKIL:K@FE F=
@EK<JK@E8C <G@K?<C@8C :<CCJ :8LJ@E> K?< @E@K@8CCP DL:FJ8C M@CCFLJ 8KIFG?P 8E; :IPGK
?PG<IGC8J@8:?8I8:K<I@JK@:F=:F<C@8:;@J<8J</:?LGG8E<K8C/FCC@;8E;&89I@
0?<FK?<IIFC<F=K?<>CLK<EI<8:K@M<0:<CCJ@JKF8:K@M8K<K?<:<CCJ8E;?<CG K?<DKF;@==<I<EK@8K<KFGC8JD8:<CCJGIF;L:@E>8EK@>C@8;@E8E;8EK@0#8EK@9F;@<J @*@IF<K8C
*=;@;??G@AB3F:A97@7E;E;@67D?3F;F;E:7DB7F;8AD?;E
0?<G8K?F>EFDFE@:>I8ELC8I%>;<GFJ@KJ@EK?<G8G@CC8IP;<ID@JF= $G8K@<EKJ N<I<@;<EK@=@<;8J<8ICP8J@E28E <I)<<I 9LKK?<K8I><KF=K?<%>
CFE>I<D8@E<;LE:C<8I%E@KN8JJ?FNEK?8KK?@JK8I><K8E;8CJFK?<8LKF8EK@><E F= $@J<G@;<ID8CKI8EJ>CLK8D@E8J<0#/UI;P<K8C0#@J8E<EQPD<
=IFDK?<J8D<=8D@CP8J0# 9LK@JC<JJ=I<HL<EKCP<OGI<JJ<;@EK@JJL<J $@KFD@
%K@JJK@CCEFKBEFNEN?PJFD<G8K@<EKJN@K?:F<C@8:GI<;@JGFJ@K@FE;<M<CFG 8EK@9F;@<J 8>8@EJK 0# $FN<M<I 0# @J ?FDFCF>FLJ KF 0# @E @KJ K?<
<EQPD8K@:8CCP8:K@M<;FD8@EJ8E;=FIK?@JI<8JFE@EK<IDFC<:LC8I<G@KFG<JGI<8;@E>
?8J9<<EJL>><JK<;8J8:FIE<IJKFE<F=0#8EK@9F;P=FID8K@FE6FE<<K8C 8E;8CJFF=K?<;<M<CFGD<EKF= $.<:<EK<M@;<E:<=LIK?<IJL>><JKJK?8K0#
8EK@9F;@<J8I<GIF;L:<;@EK?<JD8CC9FN<C$@<K@BBF<K8C8
0#@JBEFNE8CJFKF<O@JK@EK?<JB@EF=?<8CK?P@E;@M@;L8CJEFK@EK?<G8G@CC8IP
;<ID@J9LK@EK?<B<I8K@EF:PK<C8P<IJF=K?<<G@;<ID@J $@KFD@ L<KFK?<
GI<;@C<:K@FE J@K<J F= JB@E C<J@FEJ @K @J ?PGFK?<J@Q<; K?8K D@:IFKI8LD8 :8LJ<J K?<
I<C<8J<F=0#=IFDK?<B<I8K@EF:PK<J@E $6FE<<K8C"IFDK?<I< 0#
:FLC;D@>I8K<KFK?<98J<D<EKD<D9I8E<KF9@E;N@K?K?<8EK@9F;@<JCK<IE8K@M<CP 0#D8P9<I<C<8J<;@EKFK?<9CFF;JKI<8D8E;K?<@DDLEF:FDGC<O<J=FID<;@E K?< :@I:LC8K@FE :FLC; K?<E 9< ;<GFJ@K<; FE K?< G8G@CC8IP ;<ID@J 0?< 0#%>
@DDLEF:FDGC<O<J?8M<9<<EI<:<EKCP=FLE;@EK?<:@I:LC8K@FE N?@:?C<E;JJLGGFIK KFK?<C8KK<IK?<FIP#_I_><K8C
%>8E;0#8I<=FLE;KF><K?<I@EK?<G8G@CC8IP;<ID@J@E8=FIDF=@EJFCL9C<
>CLK<E;<G<E;<EK8>>I<>8K<J8E;@K?8J9<<EJ?FNEK?8KK?<0#:FCF:8C@Q<;N@K?
%>@EK?<G8G@CC8IP;<ID@JD8@EK8@EJ@KJ<EQPD8K@:8:K@M@KP08PCFI<K8C0?@J 8:K@M@KP?8J9<<EJL>><JK<;KFC<8;KF=@9I@EF><E9@E;@E> 8E;8J=@9I@EF><E@J8E
@E=C8DD8KFIP GIFK<@E @K @J GFJKLC8K<; K?8K @K :FLC; GIFDFK< K?< 8KKI8:K@FE F=
@DDLEF><E@::<CCJ0?<8::LDLC8K@FEF=0:<CCJ:FLC;K?<EC<8;KFK?<GIF;L:K@FE F=GIF@E=C8DD8KFIP:PKFB@E<J8KKI8:K@E>K?<E<LKIFG?@CJK?8K;I@M<9C@JK<I=FID8K@FE 08PCFI<K8C
0?< @DDLEFG8K?F><E<J@J @E $ @J GFJJ@9CP 8E FLK:FD< F= GIFCFE><; >CLK<E :FEJLDGK@FE@EG8K@<EKJN@K?C8K<EKFIE<>C<:K<;:F<C@8:;@J<8J</UI;P<K8C ,8K@<EK J<I@<J N@K? :F<C@8: ;@J<8J< <MFCM@E> @EKF $ N@K? FE>F@E> >CLK<E :FEJLDGK@FE?8M<9<<E;<J:I@9<;'LIGG8<K8C/8CD@<K8C 8E;@K?8J 8CJF9<<E=FLE;K?8K8><:FII<C8K<JN@K?K?<GI<J<E:<F=J<ILD0#8EK@9F;PK@KI<J
@E:F<C@8:;@J<8J</8CD@<K8C0?<<G@;<D@FCF>@:8C8JG<:KJF=K?<KNF;@J<8J<J
;@J:LJJ<;@EDFI<;<K8@C@EK?<E<OK:?8GK<I 8CJFJLGGFIKK?@J?PGFK?<J@J
' $ &#&0
::FI;@E>KF8I<:<EKD<K88E8CPJ@J K?<>CF98CGI<M8C<E:<F=J<IFCF>@:8CCP;@8>EFJ<;
8E;9@FGJPGIFM<E:F<C@8:;@J<8J<@J8E;I<JG<:K@M<CP/@E>?<K8C
%E"@EC8E;K?<GI<M8C<E:<F=:F<C@8:;@J<8J<?8J9<<EJ?FNEKF9<8J?@>?8J (F?@<K8C2@CGGLC8<K8C)LJK8C8?K@<K8C3@K?N@;<I8N8I<E<JJ 8E;@DGIFM<;J<IFCF>@:8C;@8>EFJK@:KFFCJ K?<@E:@;<E:<F=;@8>EFJ<;:F<C@8:;@J<8J<
?8J@E:I<8J<;NFIC;N@;<'8E><K8C 9LKK?<KIL<@E:@;<E:<F=K?<;@J<8J<?8J 8CJF @E:I<8J<; (F?@ <K 8C .L9@F08G@8 <K 8C 8K8JJ@ <K 8C %E
"@EC8E;K?<@E:@;<E:<F=8CCG?<EFKPG<JF=:F<C@8:;@J<8J<:FD9@E<; 8CJF@E:CL;@E>
$ ?8JI@J<E=IFDG<I @EK?<J KFG<I @EFCC@E<K 8C2@IK8<K8C.<:<EKCP 8JD8CC;<:I<8J<@EK?<@E:@;<E:<F=8;LCK:F<C@8:
;@J<8J<?8J9<<EF9J<IM<;@E"@EC8E;;<JG@K<K?<@E:I<8J@E>8N8I<E<JJF=K?<;@J<8J<
2@IK8<K8C 8E;@KN8J:FEA<:KLI<;K?8K<OGFJLI<KF8ELEBEFNEKI@>><I=8:KFI D8P?8M<GC8K<8L<;
%E K?< J K?< @E:@;<E:< F= $ @E "@EC8E; N8J FE K?< J8D< C<M<C 8J K?<
@E:@;<E:< F= :F<C@8: ;@J<8J< FCC@E <K 8C 1EC@B< @E :F<C@8: ;@J<8J< K?<
@E:@;<E:<F= $?8J:FEK@ELFLJCP;<:I<8J<;8=K<IK?<J@E"@EC8E;8E;@EK?<
1E@K<;'@E>;FD/8CD@<K8C3<JK<K8C2@IK8<K8C0?<@E:@;<E:<
F= $@E"@EC8E;@J:LII<EKCP K?<GI<M8C<E:<@J 8E;
F=:F<C@8:;@J<8J<G8K@<EKJJL==<I=IFD $/8CD@<K8C
?@C;?FF;:F<C@8:;@J<8J<@J:FDDFE 9LK8:?@C;?FF;;@8>EFJ@JF= $@JI8I<@E
"@EC8E; N?<I<FECPF=K?FJ<;@8>EFJ<;N@K? $N<I<:?@C;I<E$<IMFE<E<K8C
#CF98CCP:?@C;?FF;;@8>EFJ@JF= $J<<DJKF9<DFI<:FDDFE 8?C9FD
<K8CEK@>8<K8CFK?:F<C@8:;@J<8J<8E; $D8P ?FN<M<I <D<I><
8K8EP8><8E;K?<D<8E8><F= $8E;8;LCK:F<C@8:;@J<8J<;@8>EFJ@J@E"@EC8E;@J 8GGIFO@D8K<CPP<8IJ)8EJ@BB8<K8C2@IK8<K8C"<D8C<JGI<;FD@E8K<
FM<ID8C<J@E:F<C@8:;@J<8J</@E>?<K8C 8CK?FL>?JFD<J:I<<E@E>JKL;@<J J?FN EF ><E;<I ;@==<I<E:<J "8J8EF <K 8C 2@CGGLC8 <K 8C +E K?<
:FEKI8IP GI<M@FLJCP D8C<J N<I< GI<;FD@E8EK @E $ 8E; K?< ><E;<I I8K@F N8J
<JK@D8K<;8K)F@/D@K?<K8C$FN<M<I K?@J?8J<HL8C@Q<;@EI<:<EK
;<:8;<J K?< ><E;<I I8K@F @J GI8:K@:8CCP <M<E N@K? FECP JC@>?K D8C< GI<;FD@E8E:<
/8CD@<K8C3<JK<K8C
%&* *
*?3>>4AI7>4;ABE;7E
"FI;<:8;<JK?<;@8>EFJ@JF=:F<C@8:;@J<8J<?8J9<<E98J<;FE;<DFEJKI8K@FEF=
JD8CC 9FN<C DL:FJ8C @E=C8DD8K@FE M@CCFLJ 8KIFG?P 8E; :IPGK ?PG<IGC8J@8 =IFD
;LF;<E8C9@FGJ@<JK8B<E;LI@E>>8JKIFJ:FGP(L;M@>JJFE<K8C0?<;@8>EFJK@:
9@FGJPJ?FLC;9<K8B<E;LI@E>8EFID8C>CLK<E:FEK8@E@E>;@<K8E;DLCK@GC<9@FGJ@<J 8I<I<:FDD<E;<;;L<KFK?<GFJJ@9@C@KPF=G8K:?P:?8E><J8@8E;@8::@
0?<M@CCFLJ8KIFG?P;<M<CFGJ>I8;L8CCP=IFD8EFID8CDL:FJ8CDFIG?FCF>P8E;
KPG@:8CCP8)8IJ?:C8JJ@=@:8K@FE?8J9<<ELJ<;KFI8K<K?<J<M<I@KPF=DL:FJ8C;8D8><
)8IJ?%E8;;@K@FE I<;L:<;M@CCFLJ?<@>?KKF:IPGK;<GK?I8K@F?8J9<<EJ?FNE KF9<8JG<:@=@:D<8JLI<F=K?<;8D8><8J@K:FEJ@;<IJ9FK?K?<8KIFG?P8E;K?<:IPGK
?PG<IGC8J@80?<M@CCFLJ?<@>?KKF:IPGK;<GK?I8K@FJ?FLC;9<;<=@E<;8J8E8M<I8><
F=8KC<8JKK?I<<J<G8I8K<LE@KJ8E;I8K@FJ89FM<KNF8I<:FEJ@;<I<;EFID8C'L@KLE<E
<K8C088M<C8<K8C8
<=@E@E> @EKI8<G@K?<C@8C CPDG?F:PK<J =IFD =IFQ<E JD8CC 9FN<C 9@FGJ@<J D8P
=8:@C@K8K<;@8>EFJ@J@E;@8>EFJK@:8CCP:?8CC<E>@E>:8J<J8J 8E;Ȗį:<CCJ8I<F=K<E
<C<M8K<;@E:F<C@8:;@J<8J</8CD@<K8C8E;Ȗį:<CCJ8I<:FEJ@;<I<;8KPG@:8C
=@E;@E>@E:F<C@8:;@J<8J<8E; $/8M@C8?K@<K8C&WIM@E<E<K8C/D8CC 9FN<CDL:FJ8C8EK@9F;P;<GFJ@KJ;@I<:K<;8>8@EJK0#?8M<8CJF9<<E;<K<:K<;@E :F<C@8:;@J<8J<'FIGFE8P/Q89]<K8C8E;D8P9<LJ<;@E;@==@:LCK:8J<J8J K?<P8I<8CJFGI<J<EK@EJ<IFE<>8K@M<;@J<8J</8CD@<K8C8E;8I<8CJF;<K<:K89C<
9<=FI<K?<M@CCFLJ8KIFG?P;<M<CFGJ'8LB@E<E<K8C/@D@C8I 9LKC<JJGI<M8C<EK
>CLK<E;<G<E;<EK0#JG<:@=@:%>;<GFJ@KJ8I<GI<J<EK@EK?<JD8CC9FN<CDL:FJ8 F= $ G8K@<EKJ /8CD@ <K 8C 089C< %E "@EC8E; 8::FI;@E> KF I<:<EKCP GL9C@J?<;I<:FDD<E;8K@FEJ JD8CC9FN<C9@FGJ@<J8I<EFCFE><I@EM8I@89CPE<:<JJ8IP
=FI:F<C@8:;@J<8J<;@8>EFJ@J/<IFCF>P98J<;;@8>EFJ@JF=:F<C@8:;@J<8J<@J;<J:I@9<;
@E?8GK<ICJF F9K8@E@E>JD8CC9FN<C9@FGJ@<J@JEFKE<<;<;@E $;@8>EFJK@:J F<C@8:;@J<8J<LII<EK8I<#L@;<C@E<J
*=;@4;ABE;7E
0?<;@8>EFJ@JF= $@J98J<;FE:C@E@:8CJLJG@:@FE=FCCFN<;9P8JB@E9@FGJP0?<
;@8>EFJK@:9@FGJPJ?FLC;9<K8B<E=IFDLE@EMFCM<;JB@E:CFJ<KFK?<8:K@M<C<J@FE
@FGJP=IFDK?<<IPK?<D8KFLJJB@EFI=IFDLE@EMFCM<;JB@E=LIK?<I=IFDK?<C<J@FE
?8J9<<EJ?FNEKFJFD<K@D<JP@<C;=8CJ<E<>8K@M<I<JLCKJ6FE<<K8C0?<
9@FGJPJ?FLC;9<K8B<E;LI@E>8EFID8C>CLK<E:FEK8@E@E>;@<KKF<EJLI<K?<:FII<:K
;@8>EFJ@J8CK?FL>?K?<%>G<IJ@JKJ@EK?<JB@E=FI8CFE>G<I@F;F=K@D<"IP<K8C 0?< =IFQ<E JB@E 9@FGJP @J JKL;@<; N@K? ;@I<:K @DDLEF=CLFI<J:<E:< 8E;
;<DFEJKI8K@FEF=>I8ELC8I%>;<GFJ@KJ@EK?<;<ID8CG8G@CC8<@JG8K?F>EFDFE@:=FI $28E <I)<<I$@JKFG8K?FCF>@:8C8E8CPJ@JF=C<J@FE8CJB@E9@FGJP@JEFK E<<;<;=FI $;@8>EFJ@J8E; @=K8B<E K?<=@E;@E>J8I<EFKKFK8CCPJG<:@=@:=FI $ .<LE8C8 $JG<:@=@: JB@E @DDLEF=CLFI<J:<E:< 9@FGJP =@E;@E>J N@K? %>
?8M<9<<E8CJF;<J:I@9<;@E:F<C@8:;@J<8J< 9LKDFI<I<J<8I:?@JE<<;<;KF<CL:@;8K<
K?<D8KK<I8EE@JKI8:@<K8C
*7DA>A9K
0#N8J;@J:FM<I<;@EK?<JKF9<K?<D8@E8LKF8EK@><EF=:F<C@8:;@J<8J<8E;
$ @<K<I@:?<K8C 0?<0#8EK@9F;@<J=IFDK?<J<I8:8E9<D<8JLI<;
N@K?0#8EK@9F;PK<JK@E>98J<;FE@DDLEF8JJ8PFI9P;<K<ID@E@E>K?<<E;FDPJ@8C 8EK@9F;@<J !D N?@:? 8CJF K8I><K K?< 0# 'FIGFE8P/Q89] <K 8C %E :F<C@8:;@J<8J<0#8EK@9F;PK<JK@E>@JDFI<J<EJ@K@M<K?8E!DK<JK@E>–
MJ – 9LK C<JJ JG<:@=@: – MJ – #@<IJ@<G<E <K 8C /:?PLD8E;.LD<JJ<E!DK<JK@E>@J8CJFDFI<C89FI@FLJ8E;JL9A<:KKF
@E;@M@;L8C @EK<IGI<K8K@FE %E $ 8EK@9F;P K<JK@E> @J C<JJ 8::LI8K< 8E; K?< J<ILD 8EK@9F;@<J8I<E<>8K@M<@EFE<K?@I;F= $G8K@<EKJ)8EJ@BB8<K8C8089C<
+K?<I 8EK@9F;@<J ;<K<:K<; @E K?< J<I8 F= :F<C@8: ;@J<8J< 8E; $ G8K@<EKJ 8I<
8EK@I<K@:LC@E 8E; 8EK@>C@8;@E 8EK@9F;@<J 8E; 8EK@9F;@<J 8>8@EJK ;<8D@E8K<; >C@8;@E G<GK@;<J #,0?<=@IJKKNF8I<EFCFE><I@ELJ<8E; ,#8EK@9F;@<J8I<EFK :FDDFECP LJ<; 8J GI@D8IP 8EK@9F;@<J @E ;@8>EFJK@:J *FID8CCP K?< %> :C8JJ 8EK@9F;@<J8I<K<JK<;9LK@E:8J<JN?<I<8E%>;<=@:@<E:P@JBEFNEFIJLJG<:K<;
K?<%>#:FLEK<IG8IKJ:8E9<LJ<;8@8E;@8::@
JK?<HL8C@KPF=8EK@9F;PK<JK@E>?8J@DGIFM<; J<IFCF>P98J<;;@8>EFJK@:J?8M<
>8@E<;>IFLE;@EK?<;@8>EFJK@:JF=:F<C@8:;@J<8J<::FI;@E>KFK?<>L@;<C@E<JF=
K?<!LIFG<8E/F:@<KP=FI,8<;@8KI@:#8JKIF<EK<IFCF>P $<G8KFCF>P8E;*LKI@K@FE
@EJPDGKFD8K@::?@C;I<EK?<:F<C@8:;@J<8J<;@8>EFJ@J:8E9<D8;<N@K?FLK9@FGJP@=
K?< 0# 8EK@9F;P K@K<I @J DFI< K?8E K<E K@D<J K?< LGG<I C@D@K F= EFID8C !D GFJ@K@M@KP @J ;<K<:K<; @E 8 ;@==<I<EK 9CFF; J8DGC< 8E; K?< ><E<K@: GI<;@JGFJ@K@FE
$( - - ?8GCFKPG<J <O@JKJ $LJ9P <K 8C 0?< @DGC@:8K@FE F= K?@J
“triple criteria” has been shown to be appIFGI@8K<@E;@8>EFJ@E>9FK?:?@C;I<E8E;
8;LCKJ3<IBJK<KK<I<K8C"L:?J<K8C0?<I<:<EKCPGL9C@J?<;"@EE@J?
:LII<EK:8I<>L@;<C@E<J8CJF8CCFN:F<C@8:;@J<8J<J<IFCF>P98J<;;@8>EFJK@:@E8;LCKJ
@=K?<0#8EK@9F;PK@K<I@JDFI<K?8EK<EK@D<JK?<LGG<IC@D@KF=EFID8C8E;!D
@JGFJ@K@M<F<C@8:;@J<8J<LII<EK8I<#L@;<C@E<J $FN<M<I >CF98C:F<C@8:
;@J<8J< >L@;<C@E<J JK@CC I<:FDD<E; JD8CC 9FN<C 9@FGJP 98J<; ;@8>EFJK@:J @E 8;LCK :F<C@8:;@J<8J<(L;M@>JJFE<K8C8@8E;@8::@
%>8LKF8EK@9F;@<J8>8@EJK0#?8M<9<<E;<K<:K<;@EK?<J<I8F=K?<D8AFI@KPF=
LEKI<8K<; $G8K@<EKJ8E;0#@J:LII<EKCP:FEJ@;<I<;K?<D8@E8LKF8EK@><E@E $ /UI;P <K 8C $FN<M<I JFD< :F<C@8: ;@J<8J< G8K@<EKJ 8CJF ?8M< :@I:LC8KFIP 8EK@9F;@<J8>8@EJK0#8CK?FL>?K?<P;FEFKJL==<I=IFDJB@EC<J@FEJFIIFE@<K8C /8CD@<K8C089C<0?<<O8:KIFC<8E;M8CL<F=0#8EK@9F;@<J?8M<
P<KKF9<<CL:@;8K<;8E;K?<I<=FI<K?<J<8EK@9F;@<J8I<EFK:LII<EKCPLJ<;@E:C@E@:8C GI8:K@:<%E8;;@K@FE0#8EK@9F;@<J?8M<9<<E;<J:I@9<;@EI<C8K@FEKF>CLK<E8K8O@8
@E:F<C@8:;@J<8J<$8;A@M8JJ@C@FL<K8C
# ;887D7@57E;@6;39@AEF;5E47FI77@67D?3F;F;E:7DB7F;8AD?;E3@65A7>;356;E73E7
7D?3F;F;E7DB7F;8AD?;E A7>;356;E73E7
7@67D6;EFD;4GF;A@ *>;9:FBD76A?;@3@57;@?3>7E 7?3>7EBD76A?;@3F7 973F6;39@AE;E $AEF>K36G>FE F3@K397
*7DG? 9+3@F;4A6;7E – –
*7DG? 9+3@F;4A6;7E – –
9+67BAE;FE;@F:7E=;@ 3
9+67BAE;FE;@E?3>>4AI7> –
*?3>>4AI7>?G5AE3>H;>>AGE3FDAB:K –
3EA?7:3H7477@D7BADF763@@;EFD35;7F3>
)787D7@57E7;>7F3>#A:;7F3>G>>7F3>*3>?;7F3>ADDA@;7F3>
)7G@3>37F3>-;DF37F3>$3@E;==37F3>3
+)+$%+
>GF7@8D776;7F
JKI@:K 8E; C@=<CFE> >CLK<E=I<< ;@<K @J :LII<EKCP K?< FECP 8M8@C89C< KI<8KD<EK =FI 9FK?:F<C@8:;@J<8J<8E; $0?<98J@JF=>CLK<E=I<<;@<K@J<O:CL;@E>N?<8K IP<
8E;98IC<P=IFDK?<;@<K0?<@E:FIGFI8K@FEF=F8KJ@EK?<;@<KI<D8@EJ;<98K89C<
I<:<EK D<K88E8CPJ@J JK8K<J K?8K F8KJ 8I< @E ><E<I8C J8=< =FI G8K@<EKJ N@K? :F<C@8:
;@J<8J<8E; $,@EKF/UE:?<Q<K8C8E;@E"@EC8E;K?<D8AFI@KPF=:F<C@8:
;@J<8J<8E; $G8K@<EKJLJ<F8KJ8JG8IKF=K?<@I;@<K$FN<M<I K?<I<8I<8CJF8=<N JKL;@<JI<GFIK@E>8;M<IJ<<==<:KJF=@E:FIGFI8K@E>F8KJ@EKFK?<;@<KF=:F<C@8:;@J<8J<
G8K@<EKJI<EKQ$8EJ<E<K8C
0?< >CLK<E=I<< ;@<K ?8J D8EP =8MFLI89C< <==<:KJ FE G8K@<EKJ JL==<I@E> =IFD :F<C@8:;@J<8J<FI $0?<;@<K?<8CJ>8JKIF@EK<JK@E8CJPDGKFDJLJL8CCP@E;8PJFI N<<BJ8E;K?@J@J=FCCFN<;9PEFID8C@Q8K@FEF=8EK@9F;PK@K<IJ8@8E;@8::@
!M<EKL8CCPK?<;@<K8CJF?<8CK?<JD8CC9FN<CDL:FJ8CC<J@FEJ 9LKK?@JGIF:<JJ @J JCFN F=K<EK8B@E>CFE><IK?8EFE<P<8I.L9@F08G@8<K8C/?8IB<P<K8C 0?<JB@EJPDGKFDJF= $8CJFLJL8CCPI<:FM<I@E8=<NDFEK?JFE>CLK<E=I<<;@<K 9LK K?< ?@JKFCF>@:8C :?8E><J @E K?< JB@E G<IJ@JK @E JFD< :8J<J <M<E P<8IJ 8=K<I
@E@K@8K@FEF=K?<>CLK<E=I<<;@<K$@<K@BBF<K8C9
3BEA@7?76;53F;A@;@67D?3F;F;E:7DB7F;8AD?;E
0?<I8J?I<C8K<;KF $@JF=K<EM<IP@K:?P8E;KIFL9C<JFD<CK?FL>?>CLK<E=I<<
;@<K@JK?<:FIE<IJKFE<F=KI<8KD<EK@E $ 8JD<EK@FE<;GI<M@FLJCP K?<I8J?I<8:KJ JCFNCPKF>CLK<Efree diet. Dapsone (4,4’;@8D@EF;@G?<EPCJLC=FE<@J8E8EK@98:K<I@8C 8><EKN@K?8EK@@E=C8DD8KFIPGIFG<IK@<J0?<I<JGFEJ<=FI;8GJFE<@EK?<GILI@KLJ 8E;K?<I8J?@E $@JLJL8CCP8:?@<M<;@E8=<N;8PJ8=K<I@E@K@8K@E>K?<I8GP 8GJFE<
D<;@:8K@FE?8JEF<==<:KFEK?<JD8CC9FN<CDL:FJ8C;8D8><8E;K?LJK?<>CLK<E
=I<<;@<KDLJK8CN8PJ9<JK8IK<;8CFE>J@;<N@K?;8GJFE<%E $K?<@E@K@8C;8@CP;FJ<
F=;8GJFE<@J–D> 9LK@K:8E9<@E:I<8J<;LGKFD>;8P@=E<<;<;0F 8MF@; GFJJ@9C< J@;<<==<:KJ K?< ;FJ< @J CFN<I<; KF 8 D@E@DLD D8@EK<E8E:< C<M<C N?<EGFJJ@9C<
