CENTRO UNIVERSITÁRIO CURSO DE FARMÁCIA
DOENÇAS AUTO-IMUNES
2012 xxxxxxxxxxxxxxxxxxxxx
DOENÇAS AUTO-IMUNES
2
2012 xxxxxxxxxxxxxxxxxxxxx
DOENÇAS AUTO-IMUNES
2
2012 ÍNDICE INTRODUÇÃO.......................................................................................................................................................4 TOLERÂNCIA CENTRAL DE LINFÓCITOS T...............................................................................................6 TOLERÂNCIA PERIFÉRICA DE LINFÓCITOS T...........................................................................................9 LINFÓCITOS T EFETORES E AUTOIMUNIDADE......................................................................................13 TOLERÂNCIA CENTRAL DE LINFÓCITOS B.............................................................................................16 TOLERÂNCIA PERIFÉRICA DE LINFÓCITOS B........................................................................................16 REDE IDIOTÍPICA...........................................................................................................................................17 CÉLULAS DENDRÍTICAS E AUTOIMUNIDADE........................................................................................19
ARTRITE REUMATÓIDE............................................. REUMATÓIDE..................................................................................................................................21 .....................................................................................21 LÚPUS ERITEMATOSO SISTÊMICO............................................................................................................. SISTÊMICO............................................................................................................. 0 DIAGNÓSTICO.................................................................................................................................................30 TRATAMENTO MEDICAMENTOSO............................................................................................................32 COMPROMETIMENTO CUTÂNEO...............................................................................................................33 COMPROMETIMENTO ARTICULAR...........................................................................................................34 COMPROMETIMENTO EMATOLÓGICO..................................................................................................34 COMPROMETIMENTO CARDIOPULMONAR............................................................................................3! MANIFESTA"#ES NEUROPSI$UI%TRICAS &MNP'..................................................................................36 COMPROMETIMENTO RENAL.....................................................................................................................3(
ESCLEROSE MÚLTIPLA !EM"........................................................................................................................42 DIAGNÓSTICO.................................................................................................................................................43 Critérios de Poser:........................................................................................................................................43
TRATAMENTO......................................................................................................................................................44
DIA#ETES MELITO TIPO 1.............................................................................................................................4$ DOENÇAS TIREOIDIANAS AUTO-IMUNES.................................................................................................%2 PATOG)NESE DA AUTOIMUNIDADE TIROIDIANA................................................................................!3 TIREOIDITE DE ASIMOTO................................................................................................................................!! DOEN"A DE GRA*ES...........................................................................................................................................!6
MIASTENIA &RAVIS.........................................................................................................................................%$ ESCLERODERMA...............................................................................................................................................%' ANEMIAS AUTO-IMUNES................................................................................................................................%( ANEMIA )EMOLÍTICA AUTO-IMUNE.........................................................................................................%* SÍNDROME DE &OODPASTURE....................................................................................................................$0
3
INTRODUÇÃO N+, -/+, +5/, 8:/,;/<=><+, / ,,?5<+,@ ,/+:,/ ;/-+ -+ <+;+<-+-/ - ,,/5+ 58< - -=- /5 -,8 / ;; & self ' -+ / ;; & non-self '. E,,+ <+;+<-+-/@ -/5+-+ +/<+@ 5+-+ +, <+, 5<5;///, B / T + ; 5/<+,5, <,. 11 A ;/-+ -+ +/<+ ;-/ / <+,+, =,/<+, /=,/<+,. C+,+, =,/<+,@ , @ /+<+-+, + <++</=,<+, - ;; -=-@ /, /5 8/+ +,,<+-+, + ;5>,5, -/ 5<+, -/ H,<5;+-+-/ <5;//, -+ 5-+-/ ++ <5 ,,/5+ C5;/5/ / /<, <5 +-+-/ /8++ / <<+, +5 -/ >+/, H5+,@ / /, , </ 8/<. F+/, +5/+, <5 >/<J/, +</++, / +,@ /;, + +8//, >=,<, / =5<, <5 U*@ ;/,<-+, / -8+, , //5;, -/ <+,+, /=,/<+,.11 E,-, /;-/58<, ?5 -/5,+- + 5;<+ -/ >+/, 8/<, + ,,+5+@ + ++ -/ <<-<+ ;++ -/+, +5/, 5+ /5 8?5/, 5K8<, - / /5 -K8<,. E/+@ 5/,5 /5 5 -=- 8//<+5// ,,++ - + ;+<;+5 + >+/, =,/<, + /=,/<,. A 5;<+ -+ +,,<+ -/ >+/, +5/+, / 8/<, ;-/ ,/ +++-+@ ; //5;@ + -/+ ///, +, +,,<+J/, // >/< / /+/<J/, ;-/5 -/,/<+-/+ + ;/-+ -+ /<+ ; , 5/<+,5,. E/ //, ;-/5, <+ -+ /<-+ / /<,/
4
O //5; <,,< -/ 55/,5 5/<+ + >// /5<+ +;, >/< ; /,/;<<, Q:H/5=<, - 8; A@ + + +<;, <+ + ;/=+ M - /,/;<< / /+8/5 <K+-+5// <5 /<- <+-=+< , /<+-, , -/ ;+<//, <5 >// /5<+. A;;,/@ ;<+@ + </ -+, ;;+J/, ><+, 8/+-+, <, -/ 5+ /,;,+ 5/. U5 +5/ + ++ -/ +;;,/ ;-/ /,+ /5 5-/><?<+, / H +, /-?<+, -/ / >+H+, , 5/<+,5, -/ +;;,/ clearance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
TOLERÂNCIA CENTRAL DE LINFÓCITOS T *, +,;/<, , //+/, + <,-/+5, + /+ -, 5/<+,5, -/ /<+ <5 <,/// -/,/<+-/+5/ / 5+/ -/ +5+-+-/, +5/,. U5 -//, + +/K+ 5>++ / ;8?<+ -, +-, +5/,@ /,- + 8//, <+-, ,,<+ +, 58+, -, ><, B &LB' / TCR -, ><, T <' ,/+5 +/+,@ //5 5-><+J/, ,//<+, /,+, <++</K+- , ->///, /,8, -/ ->//<+ -, LT. N+ /+;+ <+ -+ 5++ H ;>/+
/8 5+, //+ - </@ /++ -, 8//, - TCR / /;/,, -+, 5<+, -/ CD3@ TCR@ CD4 / CD( + ,;/>=</ +8, / <+, -/-=<+, -/+-+, -+ 5/-+ ,,/+ +5 -/ >+,, / 5<+, -+ 5+K /+-+5/+ ;++ + ;>/+@ + ->//<+ =</@ <5 CD4 / CD(@ / + <+ - /;/ -/ ////,@ ,// ;,+ /@ ;,/5//@ /8++. O ;<+, ;++ ;/;=-/, /;,, +, 5<+, -/ MC -/ <+,,/ I /@ +, CD4 Y@ /,;/<=><+, ;++ ;/;=-/, /;,, ; 5<+, -/ MC -/ <+,,/ II. A ,// /8++ ;/5// + <5;/ ;/;=-/:MC ;; , /5+-,@ /+- +,,5 + 5++ -/ LT +/+,. E5 /,/@ ;; & self ' 58< <5;//-/ -, , /;=;, &-//5+/, +8?<,' <-><+-, ;/ DNA - -=-@ -/ 5- / -, , -/5+, /;=;, ,/+5 /<H/<-, <5 ;;,. D+/ - ;
7
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/8++, -/ <?<+ ++ T REG,.
TOLERÂNCIA PERIFÉRICA DE LINFÓCITOS T
9
A /<+ 58<+ +, +=8/, ;;, & self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
>+/<,.11 A - LT ;-/ ,/ +55 -+ ;/+ 8+ -/ 5+ 5<+ <5;/-+ -+, 5<+, </,5++, -+ >+5=+ B7. E5 -//5+-+, <-J/,@ +, APC, ;+,,+5 + /;/,,+ + 5<+ CTL:4 &CD1!2'@ / /5 5+ +>-+-/ + CD2( / +, 5<+, B7 &CD(6 / CD(0'. N /+@ + < -/,,+, 5+,@ + CTLA:4 /5 + + ,/ , LT@ -K- ,+ +;;,/. O / -+ 5<+ CTLA:4@ /5 <+5-8,@ + 5/8+-+@ / +;/,/+5 <5 <++</=,<+ ,<+ + <+;+<-+-/ -/ ;- -/ <<+, 5,,;/,,+,@ <5 IL:4@ IL:10 / 5TGF:Q@ +5 -+ <+;+<-+-/ -/ - -/ ,;/,, 5/-+-+ ; <+ <+:<+ ; /5- -/ 5<+, -/ ,;/>=</ <5 CTLA:4. C+, <5 > 5/8+-+ /, /-+, + 5-+ / </ -, ;+5++,@ <-J/, / >+/// +, -/,, +=8/, ;///, -/ +8//, >/<<,,@ 5/,@ ++=8/,@ ++=8/, / +8/,. E/ , LT <5 > 5/8+-+ /5, +, células T reguladoras de ocorrência natural &TREG, CD4Y CD2!Y CD127 LZ@ F;3Y'@ <+5// -/,<+, ; S+[+8
;- -/ IL:10 / ,;5/5 -/,/5/
-/ +85+, /,;,+, -/ LT in vivo" / +, células T#3"<+;+K/, -/ ,;5 <+,:+ 5/-+/ + ;- -/ TGF:Q. E,/5 +-+ +, +, <+, <5 > /8+-+@ <5 , LT CD( YCD2(:@ <+, N\]T@ <+, T WX@ LT -;:/8+,@ LT CD( Y$+1Y / <+, B CD1Y. A, ;<;+, <+, <5 > 5/8+-+ /, /,/5+K+-+, + F8+ 3.
11
A //<+ -+, ;;+J/, <,. A/, ><+,@ >/=;<, / ++, -/ <+, /8+-+,@ ?5 ,- /++-, /5 +, -/+, /5<+, +5/, H5++,@ /-/<+- +,,5 ,/ 5;+/ ;+;/ + 12
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
LINFÓCITOS T EFETORES E AUTOIMUNIDADE //, CD4 Y <5/++5 + ,/ <+/8K+-, /5 -, ,;, -,,@ T $el%er 1 &TH1' / T $el%er 2 &TH2'@ 5+- ; +,/ ;+- -/ <<+, ;-K-. A8, +/, +K++5 +-+ + /,?<+ -/ 5+ /<, ->//<+-, <+;+K/, -/ ;-K <<+, - ;/> TH1 / TH2. A+5// /, <+ /@ +;, + /,5+ +8?<+@ <>5/ +5// <+ -/ <<+,@ , LT CD4 Y naive ,/ ;>/+5 / ,/ ->//<+5 /5 ->///, ,;, />//, <5 <++</=,<+, ;;+, &TH1@ TH2@ TH3@ T REG@ TH17'@ -//5+-+, ;/ ;/> -/ <<+, ;-K-+, / ;/+, ;;/-+-/, ><+,. C>5/ /,/5+K+- + F8+ 4@ +, <+, TH1 <++</K+5:,/ ;<;+5// ;/+ ;- -/ 8+-/, +-+-/, -/ INF:W@ /+ +, <+, TH2 ;-K/5 IL:4@ IL:! / IL:13. A, /,;,+, TH1 -/,/<+-/+5 , 5/<+,5, -/ H;/,/,-+-/ +-+@ ++5 13
5+<>+8, / , 5 /><//, + /5+ -/ ;+8/, +<//, /5 ++ + /,;,+ 5/ H5+@ -/,/<+-/+- ;- -/ 58+, / >+5+ /,>=<+@ /,;,+, /,+, 5+, 5;+/, <5+/ +, ;+8/, /+<, TH0 //5 ;++ ->//<+ TH1 TH2 +-+ /5 5 /,8 <+ -+ ++ TH1 TH2 -/<+5 ;++ -/,/5/ -/ ,+ /,;/<+ +@ - + /;/,, - ;+- ;,. D/,/ 5-@ 5+ /K ;+K+-+ + /,;,+ 5/ ;++ ;+- TH1@ + + TH2 ,/ -+@ / //<+ -/ >+/, -/ +,< / -/ 5-++, /;8/<+,. 11
A, /,;,+, 5/, />/+, -/,/8+-+,@ /++5++, / ?5 ,- +,,<+-+, - / ;8/,, -/ -/+, +5/,. E/+@ /,-, /5 <+5-8, +,8?<,@ -/><//, -/ INF:W -/ ,/ /// /,,?<+ + -/,/5/ -/ +5-+-/. A <@ /,,/, +5+, ,/ +;/,/+5 + 5+, ,,
,/+J/, /++5 + /,+5/ - ;+;/ /<, -+, <+, TH1 + >,;+8+ -/ -/+, +5/,@ +- ;/,;/<+, ;++ + ,<+ -/ ,; -/ LT@ -, -+ ,;;+ TH1@ <+;+K -/ -K >+5+ /<-+ / +5-+-/. A //5-+-/, >+5++, <`<+, / -/,/5/ -/ /,-, ,/ ;;+J/, -/ LT />//, /++5 <++</K+ -/ LT ;-/, -/ IL:17@ -/5+-, ><, TH17. P/,,+, /<+ -/ ><, T CD4 Y ;-/, -/ IL:17@ 5+, - / <+, TH1@ ;,, 5 ;+;/ +5++ /,+@ /,;-/ +,+/ / +/ -;<+ / -/5,++5 + ;/,/+ -/ =/, //+-, -/ ;-, >+5+, /+<+-, + />/+ TH17 5/,5 + ,+ ;+<;+ -/+ , 5/<+,5, >,;+8?<,. O, <+5++, <`<+, +;+5 ;++ ;+;/ +5+ /<-+ ;/<+5++, / 5<+, /,;,/, ;/ /<+5/ -/ <+, TH1 +, ,=, >+5+,. M/,5 / <+, T /8+-+, &T REG,' ,/ +<5/5 +55 /,,/, <+,@ + ;/,/+ -/ +, =/, -/ <<+, >+5++, + +, <+,:+ 5/, ,,/-+-/ ;8+5+ -/ ->//<+ -, LT CD4 Y@ /,- 5+ /,/+ +,,<+ // + + TH17 / +, +, TH1 / TREG. D/;/-/- -+, <-J/, -/ /,=5 / - 5/ + ,/ /<+5@ +, <+, TH17 ;-/5 ,/ ->//<+ + /5 <+, TH1 <5 /5 <+, T REG,@ / +/+ ,8><++5// /,+- >+ -+ /,;,+ 5/. D/ -/,/ </ ++@ 5+ + ,;;+ -/ LT />//, > ;;,+@ +, <+, TH9. O, ><, TH9 >+5 /<, TH2 /,5+-, + ;/,/+ -/ TGF:Q / IL: 4@ / / +;/,/+5 /H5 -, >+/, -/ +,< <++</=,<, -+, +, TH1@ TH2@ TH17 TREG.17 O ;+;/ -+ IL:9 /5 ,- 5 /5 -<5/+- + >,;+8+ -+, <-J/, +8<+, <`<+,@ /+@ 5 ;< ,/ ,+/ ,/ ;+;/ -/,,+, <+, +, -/,+, -/+, H5++,. 11 1!
A <5;//, -/,+, +, -/ ->//<+ / -/ ,/, -/,/=, +, +, />/5-+-/, +5/, ;-/ +-+ -/,/5/ -/ /,+8+, /+;?<+, / ,+5 + +5;+ + + -+, <+, /8+-+, +5// <5 </ -+ /,;,+ >+5++ />/+.
TOLERÂNCIA CENTRAL DE LINFÓCITOS B $+- +, 58+, -/ 5/5++@ , //+@ /,/5 5/<+,5, -/ /<+ +H+ + /5+ -/,,/, ><,@ /,/5 +55 5/<+,5, -/ /<+ ;/><,. D/><?<+, /,,/, 5/<+,5, ;-/5 /+ + -/,/5/ -/ +5-+-/. O, LB 5+, / /<H/-+-/ + 5/-+ ,,/+ , /5+-, ,>/5 /++ -, 8//, RAG1 / RAG2 &/ <+,+5 H;/5+ ,5<+ +, /8J/, H;/+/, -, 8//, -/ 58+,' / /;/,,+5 5+ + <+-/+ -/ 58+@ +;/,/+- 5+ + /,;/<><-+-/ +8?<+. E,,/ ;+H+ /5 /5+ + +/+-+-/@ +, <+, ,@ /5 8/+@ -//+-+, ; +;;,/ &F8+ 1B'. E/+5// LB / /<H//+@ ;5 +;/,/+- ++ /;/,, -/ 58+, -/ 5/5++.
TOLERÂNCIA PERIFÉRICA DE LINFÓCITOS B E/+, LB +/+, 5+-,@ + /<+ ++=8/ ,/ + ;/>/+ + +,?<+ -/ LT ++/,@ , @ - ,/8- ,+ -/ ++@ +5:,/ +8<,@ 5;,,+-, -/ /,;-/ +;, , /<, <5 +=8/. S/ 5 LB +8< /<+ 5 LT ++ ++-@ ;-/ ,/ /5+- ;/+ /+ // F+, - LB / F+,L - LT. N+ +,?<+ -+, +, 5+, -/ </,5+@ , ><, B +8<, -/5,+5 5+ ,/,-+-/ +;;,/ +;, + 8+ - F+, + ,/ 8+/ &F+,L'. N/,,/ </@ + /;, <`<+ +, ++=8/, /5 +5// >,8< & >+5+' ;-/ < ;++ + 5+/ -+ /<+. 11 16
LB / /<+5 ++=8/, + ;/>/+ <,/8/5 ,/ -5<+ , >=<, >-/,@ ;+/5// ; >+H+, + /;/,, -, /<+ ;++ LB / -/,//5 /,;/<><-+-/, +/++, <5 /,+- -+ H;/5+ ,5<+@ -+/ 5+ /,;,+ + 5 +=8/ /,+H@ , +K+5 >+ -/ / + 5/+ /,?<+ -/ LB +/+,@ /5 ,@ /,+. A/, / 5+ /,;,+ 5/ ;,,+ ,/ <+-+@ , LB ;/<,+5 /<+ ,/, +=8/,@ // -, LT@ / ,/ 5+ -/ ,+K+ +
REDE IDIOTÍPICA A /+ -+ /-/ -=;<+@ -K-+ + -<+-+ -/ 1970@ ,/ +,/+ + /+ /<=;<+ // +, /8J/, +/, -, +<;, ;-K-, ; 5 -+- -=-. O -; + ; -+ /8 +/ -+ 5<+ -/ 58+ / /+8/ <5 +=8/. C+-+ -; ;-/ ++ <5 +<; >// + +=8/ / /<H/// + 5 +<; +:-;. 19 E,/ 5+ 5+ 5+,,+ <=<+ / < ;++ + /,+-+-/ - ,,/5+. E,=5, +8?<, /=,/<, /;/,/++5 -,, /,,+ 5+H+@ 5+, /-/+5 + ,/ +,,5+-, <5 / + status &uo. E5 /,/@ ,,/5+ 5/@ + /-+-/@ //8++ ;/-5+/5// + , ;; / + /,;,+ + 5 +=8/ /,++ +5/ -/ 5 -//5+- +<; -+ /-/@ <+,+- 5+ ;/+ + H5/,+,/ - ,,/5+. O +5/ - ;5/ +<;@ AB1@ /<H/<- ; AB2@ /++ + 5 +5/ -/,/ 5@ / /-/+ + ;5/ 5+ H;/8+ - ;5/ &AB1'. O 5/,5 +</
17
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CÉLULAS DENDRÍTICAS E AUTOIMUNIDADE A, <+, -/-=<+, &DC,' , <+, - ,,/5+ 5/ / ?5 <5 ;<;+ > ;-+5/+ + 5+/ + -+ /<+ <+. C+,,<+5// +, DC, ;-/5 ,/ ---+, /5 2 ,;, ;<;+,@ 5/-/, / ;+,5<-/,@ / ->//5 /5 ,+ 8/5@ 5>8+ / ;-, ,/</+-,. A, DC, 5/-/, &5DC,' , 8+-/, ,/</+, -/ IL:12 / +, ;+,5<-/, &;DC,' -/ INF:V. 11 A, DC, , /<+-+, , 5+, -/,, ,=, ++`5<, /@ 5+ /K ++-+,@ 58+5 ;++ 8, >-/, ,/<-, -/ /+8 /,+5// <5 LT / LB. A, DC, ?5 5 ;+;/ . D+/ >/<J/, +,@ 5<5;/, </- DNA RNA -/ <+, +;;<+, /<<+, , /+K+-, ; DC, / LB@ /+8- <5 , /5+5 ;+;/ <=< - INF:V + /;+8/+ -/ -/+, +5/,@ ,8/- / + - -/ +5-+-/ // /+/, <5 55/,5 5/<+@ 5+, ;-/ /,+ /+<+-+ +;/+, + /, /<-+ / ++ -+ /,;,+ 5/ ++ /5 -=-, ,,+5++,@ /,;/<+5// />/, ; I &INF:V / INF:Q'.11
19
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A+,+, +/,3 A AR 5+ -/+ 55/-+-+@ <5 >,;+8+ +,+/ <5;/+. A</-+: ,/ / // <+ ,/+ ;+/5// + ++ -/ <+, T -/;/-// -/ +=8/,@ -/,/<+-/+- 5+ /,;,+ 58<+ /,,/<+5// - ; TH1. E,,+ ++ /+ + 5;, />/,@ <- ++ / ;>/+ -/ <+, /-/+, / ,+,@ /<+5/ / ++ -/ <+, ;:>+5++,@ ,/</ -/ <<+, / ;/+,/, + ;+ -/ 5+<>+8, / <+, ,+, >+,,: like / ;- -/ ++<;,. 6 C++</K+-+ ; ;+/ ;/><+@ ,5<+@ / /+ + -/>5-+-/ / -/, -+, +<+J/, /5 -/ -/ /,J/, ,,/+, / -+ <++8/5. A>/+ 5H//, -+, + ?, /K/, 5+, - / H5/, / ,+ ;/+?<+ +5/+ <5 + -+-/. E5 8/+@ + AR +<5// 8+-/, / ;//+, +<+J/, /5 +,,<+ <5 5+>/,+J/, ,,?5<+, <5 8-/K 5++@ >+-8+ / ;/-+ -/ ;/,. $+- // , 8,@ + 5-+-/ / + 8+-+-/ -+ -/+ , 5+/,@ ;-/- -5 + /;/<++ -/ -+ /5 << + -/K +,. C5 + ;8/,, -+ -/+@ , ;+<//, <5 AR -/,//5 <+;+<-+-/ ;++ /+K+ -/ ,+, +-+-/, + -/ -+ -+ <5 ;>,,+@ <5 5;+< /<`5< ,8><+ ;++ ;+<// / ;++ + ,</-+-/.
Diagnóstico O -+8,< -/;/-/ -+ +,,<+ -/ 5+ ,/ -/ ,5+, / ,+, <=<,@ +<,.
C+,+56 789:756 8;5+,5+6 A /+ ;++ -+8,< +,/+-+ , <, -/ <+,,><+ - C8 A5/<+ -/ R/5+8+ 1 1. R8-/K 5++ 8-/K +<+ -+- ;/ 5/, 5+ H+ 2. A/ -/ ?, 5+, /+, ;/ 5/, ?, /+, +<+/, <5 /-/5+ -/ ;+/, 5/, -/+5/ +<+@ ,/+- ;/ 5-< 3. A/ -/ +<+J/, -+, 5, &;H@ />++8/++, ;5+, / 5/+<+;>++8/++,' 4. A/ ,5<+ !. N- /5+-/ 21
6. F+ /5+-/ &FR' ,<. 7. A/+J/, +-8><+, /,J/, -/,<+<><+J/, <+K+-+, <+K+-+, /5 +-8+>+, -/ 5, / ;H,. O, <, -/ 1 + 4 -//5 /,+ ;/,//, ;@ ;/ 5/,@ ,/, ,/5++,. O/+ ;++ <+,,><+ + -, ,// <, , /<+ 5 ;+<// <5 /- AR. O,/+ ;+<//, ;+<//, <5 -, ?, <, , /<=-, -+ ;,,-+-/ - > -/,/5/ -/,/5/ -+ -/+@ ,/- <,-/+-,@ <-@ ;++ <, /,,/ ;<. 1
A+,+, +/,ide inicial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<5;5/5/ /+:+<+ / -/ /, +-8><+ &$+- 1'. E,;/<+ +/ -// ,/ -8-+ ;++ + -/><+ -, ;+5/, ,8/,, -/ 5+ ;8,< &$+- 2'.
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24
TRATAMENTO
Consid!a"#s g!ais O -+8,< ;/<-+5/+, ;++ </ -+ +-+-/ -+ -/+ / ;++ ;// <+;+<-+-/ ><+ / /, +<+ //,=/.1 O, /, ;<;+, - ++5/ - ;+<// <5 AR , ;// <+ + /, +<+@ ;// + ;/-+ -/ > / -5 + -@ /+- 5+5K+ + +-+-/ -/ -+ -/,,/, ;+<//,. A /5,, <5;/+@ +;/,+ -/ ,/ / >+ - ++5/@ ++5// +<++-+. 1 O ++5/ <5/+ <5 + /-<+ - ;+<// / -/ ,/, >+5+/, ,/ ,+ -/+@ +, ;,,-+-/, -/ ++5/@ <5 ,/, ,<, / //>=<,. O +<5;+H+5/ 5-,<;+ ///<+5// , + /+ - /5+8,+. 1 O ++5/ -+ AR -// ,/ <,-/+- 5 ;
T+,:,5 :>5 37:,565 M37: ?967 +;8,=>5 :5 ,+,:,5 3 AR C,-/+- ;/<+ <+;+<+/ -+ AR@ +<5;+H+5/ -/,,/, ;+<//, - ; -/ ,+ ><+ -// </ -/,-/ =< -+ -/+ <5 /+ + ;+<// / ;8+5+, /+;?<, -8-, ;/ +<+@ 5+/ - /,+- ><+ - +;+/H <5 / - ,,/5+ <+-/,;+. F,/+;+ / /+;+ <;+<+ </5 ;++ / ;+<// ;,,+ <+ + //+/<5/ -+ 5,<++ ;/+<+ / +-/+- ;8+5+ -/ >/-+-/@ /+- /
O <-<+5/ >=,<@ //- +-+-/ +/<+@ //<=<, /,,-,@ +8+5/, / /++5/@ -// ,/ /,5+- ,/+-:,/ , <, -/ /<+ + //<=< / >+-8+. R/, -, 55/, a /,/, a /5 <5 / ++ +, -/, 5+<+/, ; /,+K+ +<+@ </ / /+H+5/. S+ K+ -// ,/ /5//@ //+ , /,/, ;++ , ;,. O ;+;/ - /;, / - //<=< -// ,/ />+K+-@ /<H/<+.
T+,:,5 37:,565 A /+;?<+ - ;+<// ++ -/ +<- <5 /,8 -+ -/+@ ,+ +-+-/ / 8+-+-/.
S:,5@,756: P++ </ -+ - / - ;+5+ +<+ , -/ +:>+5+, H5+, &AIN,'@ +,,<+- + -,/, ++, -/ 8<<<-/, &+ 55 1! 58 -/ ;/-,+'@ 5 5;+/ +-+/ /+;?<+ -/ +,/. P+<//, / ,+ 8<<<-/, ; /5; ;8+- &5+, -/ ?, 5/,/,' -//5 ///+ -+ /><<+ // , -/,, AIN, -,;=/,. /+/, -/ ,< -/ <+-+ ;+<//. O, -/, ,//, -/ COb:2@ -/ <, 5+, //+-@ +;/,/+5 5/, />/, +-/,, 8+,/,+,. C5 /+ +, />/, <+-+,<+/,@ , /,-, -/5,+5 ,< +5/+- + ;++ , -/, ,//, + ;++ , AIN, +-<+,@ -/ >5+ / -, , AIN, -//5 ,/ /5;/8+-, /5 5//, -,/ / /5; /+J/, <5 8<<<-/, /, -<+-+, , <+,, -/ 5 8+/, ;/,,//,. 26
T++5/ -+ +/ /5+-/ <+ c A++ , -/ +:>+5+, H5+, / ++8,<, c I<+ DMCD &5//+]<+]H-<+] ,>+,,++K+]/>5-+' c C,-/+ , -/ 8<<<-/ /5 ++ -,/@ ; + +@ >+ +:+<+.
T+,:,5 <58/,<5 N H+/- /,;,+ <=<+ <5 -,/, 55+, /+-+, -/ MTb + ;/,/+ -/ />/, +-/,,@ /<5/-+:,/ + <+ @ ;/>//<+5//@ , -/ <5+J/, -/ DMCD. A, <5+J/, 5+, K+-+, , MTb <5 <+@ <5 ,>+,,++K+ + +,,<+ -/,,+, ?, -8+,. P-/:,/ <,-/+ + ;,,-+-/ -/ , -/ MTb <5 />5-+ MTb <5 <<,;+. N+ ;/,/+ -/ 5+>/,+J/, /+:+<+/, 8+/, ,/ ;-/5 K+ ++, -,/, -/ 8<<<-/, ; + + &1 + 2 58][8]-+' + >5+ -/ ;,/+;+. A K+ -/ <<>,>+5-+ ><+ /,+ //, <+,, -/ 5+ 8+-+-/ &F8+ 1'.
27
'igura ! - (lgorit)o %ara o trata)ento da artrite reu)atoide.
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
29
L/6 +,,565 66,75 O ;, //5+, ,,?5< &LES' 5+ -/+ >+5++ <`<+@ 5,,,?5<+@ -/ <+,+ -/,<H/<-+ / -/ +/K+ +:5/@ <++</K+-+ ;/+ ;/,/+ -/ -/,, +:+<;,. E <5 5+>/,+J/, <=<+, ;5><+,@ <5 ;/=-, -/ /++/, +5/+,@ <5 K +/+ / +8, 5/-<+5/,.9 LES 5+ -/+ ++@ <-- 5+, >/d//5// /5 5H//, /,@ ,/+@ + >+,/ /;-+@ 5+ ;; -/ / + -/K 5H//, ;++ 5 H5/5@ / <5 ;/+?<+ ++- -/ 14 + !0]100.000 H++/,@ /5 /,-, /:+5/<+,. A -/+ ;-/ </ /5 -+, +, ++, / /5 -+, +, ;+/, - 5-.
DIA$NÓSTICO N+ ;<+@ <,5+:,/ /,+//<+ ;;,, ;/ A5/<+ C/8/ > RH/5+8e &ACR'@ / ,/ +,/+ + ;/,/+ -/ ;/ 5/, + <, -, K/ <+-, + ,/8 &T+ / +.@ 19(2 / + /5 /8 5++@ ;++ /5 //. 2' L/, -,<-/ /, //5+,+@ >+-+@ <5 /,<+5+, /+<+, +-/-+, / +5;J/, ><+/,@ / / <5 <<+K +><+ / -,<5+. 3' F,,/,-+-/ /+/5+ </@ <5 /+ ,+ /;, K ,+@ -/ +<- <5 + H,+ - ;+<// <>5/ ,/+- ;/ 5-<. 4' f+=8/+,@ ,+5// -/,@ ,/+-+, ;/ 5-<. !' A/ +/ /,+ //- -+, 5+, +<+J/, ;/><+,@ <++</K+-+, ; - / /-/5+ -/+5/ +<+. 6' S/,/ ;/, &<++</K+-+ ; H,+ <
30
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
MEDIDAS &ERAIS C5 ;+/ 5;+/ -+ +-+8/5 /+;?<+@ +85+, 5/--+, 8/+, , /<5/-+-+,@ -// /+, 9 31
1' E-<+ >5+ + ;+<// / +, >+5+/, / + -/+@ ,+ /@ ,/, ,<, / /<,, -,;=/, ;++ -+8,< / ++5/. R/<5/-+:,/ + /=,<+ /;, , ;/=-, -/ +-+-/ ,,?5<+ -+ -/+ / 5/--+, ,+- + 5/H+ - <-<+5/ >=,< &/,5+ +-+-/ >=,<+ /8+'. 4' D/+ N H /-?<+ </=><+ -/ / , +5/, ;,,+5 >/<+ -/,/<+-/+5/ / -+ -/+. R/<5/-+:,/ + +- -/ 5+ -/+ ++5+, -/ +-+ +/+. 6' E+ ++8,5.
TRATAMENTO MEDICAMENTOSO O ++5/ 5/-<+5/, -// ,/ --+K+- ;++ <+-+ ;+<// / -/;/-/ -, 8, ,,/5+, +<5/-, / -+ 8+-+-/ -/,,/, +<5/5/,. E5 ;+<//, <5 <5;5/5/ -/ 5;, ,,/5+,@ ++5/ -// ,/ /+- ;++ 5+, 8+/. $+- H/ 5+>/,+ / /,;-+ + 5+ -8+@ ;-/ ,/ /+K/ , <<5+/ -/ -/,, 5/-<+5/,. P //5;@ ;+<// <5 />/ / /,J/, </+, ;-/ //@ +,,<+- + , -/ +-5-+ ;++ ++5/ -+ /, </+ />++. I-/;/-// - 8 ,,/5+ +>/+-@ , <= -/ +5+<, &->,>+ -/ <+ 4 58][8]-+ ,>+ -/ H-<+ 6 58][8]-+' -<+- <5 + >+-+-/ -/ /-K + +-+-/ -+ -/+ / /+ ;;+ <<-/ /5 -, , ;+<//, <5 LES. M/H+ - ;/> ;=-< / /- - ,< -/ 5,/ , //>=<, +-<+, +=-, + , -/ +5+<,. 9 A5 -, +5+<,@ , 8<<<-/, &GC' , +, -8+, 5+, K+-+, ++5/ - LES. A -,/ -/ GC ++ -/ +<- <5 + 8+-+-/ -/ <+-+ <+,. D-+<+5// +, -,/, -/ GC &/- + ;/-,+ <5 ;+-' ;-/5 ,/ ---+, /5 D,/ ++ 0@12! 58][8]-+ D,/ 5-/+-+ 0@12! + 0@! 58][8]-+ D,/ ++ 0@6 + 1 58][8]-+ 32
D,/ 5 ++ 1 + 2 58][8]-+ P,/+;+ <5 GC / +/,+ -/ 18 -/ 5/;/-,+ &1!:20 58][8]-+' ; ?, -+, <,/<,. 9 E5 -/ -, 5;, />/, <+/+,@ , GC -//5 ,/ K+-, + -,/ />/+ ;++ </ -+ +-+-/ -+ -/+@ /@ +,,5 / ;,,=/@ >+K/ /- 8+-+ -/ ,+ -,/. E5+ H++ 8+-/ ++-+-/ --+ + ,/,-+-/ +, GC@ /, -/5,+- / , -/ GC -/ 8+ +@ <5 + -/+5/+,+ 5+, -//@ -//- ,/ /+- ,/ , -. N, ;+<//, / <,/8/5 +8 5+ -,/ -/ 5+/ -/ GC +//<+ // +-+-/ -+ -/+ / >/<@ /5+- -+ ;,,-+-/ -/ </,?<+ -/ +5+,@ +,,5 <5 -+ ;/,/+ -/ <:5-+-/,.
COMPROMETIMENTO CUTÂNEO O ++5/ -/;/-/ -+ //, - +<5/5/ -/5+8< / -+ 8+-+-/ -+, 5+>/,+J/, /+:</+,. É 5;+/ /5+ / /5 -+ /, </+ /,;/<=><+ ;++ ;,@ ;-/- -/</ -/ <5;<+J/, - ++5/ -/ +, -/5+,/, <<5+/,@ ///- <-+, -+8,<+, / /+;?<+, -/,+,.
FOTOPROTEÇÃO C,-/+- / + +-+ +/+ B + ;<;+ <+,+-+ -/ >,,/,-+-/ / -/,/<+-/+/ -+, /,J/, </+, - LES@ ;//, ,+/, <5 FPS 1! 5+, -//5 ,/ K+-, /5 +-+-/ 8//,+ ;/+ 5+H / /+;<+-, 5+, 5+ /K + -+. O , -/ /+-/, ,+/, -/ +5; /,;/< ;-/ +K/ //>=< +-<+ ;/+ <+;+<-+-/ -/ ;/ <+ U*:A /5 +85+, /,J/, </+, <5 +, /,J/, ,+8-+,. N+, /,J/, </+, <+K+-+, /, -<+-+ + /+;+ ;<+ <5 <<-/ >+- + >+/. E5 /,J/, 5+, H;/><+,@ -<+:,/ <<-/ >+-@ ;-/- ,/ +;<+- , + >5+ <,+ -/ >+.
33
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34
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37
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39
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41
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44
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A ;/,/+ -, +<;, -/+ 5 DM -/ /8+ +:5/ /@ ;+@ - ; 1 <,,<@ -/5+- -/ ; 1A. D/,, 5-, >+5 <+-, ;++ + 5/--+ -, -/,, AC, /5 <++J/, /+<+, ;++ ,+ ;+-K+. C5 H ;+-K+ /+<+ - +<; <+ +=8/ -/ ,;/>=</ -+, H+,@ / ;+<+5// /,/5 /,-, <5 /,+-, <,,//, / /;-=/,@ ,+ K+ 5+-+ ;/,,+. O, AC +:H+,@ +-/,<++,/ - <- 85< / +=8/ - I,5+:2 ;,,/5 /,+, +,/+-, /5 ;/=+, /<5+/, / ;-/5 ,/ 5+<+-+, <5 - +-+@ ;,,+- +,,5 -/,/5/ -/ /,+, 47
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
;+, versus >H, -/ 5/, <5 DM ; 1. N ,iabetes Prevention Trial &DPT:1'@ > 5+<+- 5+, ,/,=/ -/ -//< -/ 5;, +<;,. N /+@ ,+/:,/ / /H5 +<; ,+-+5// ;/-K -/ >5+ ,+,>++ ,< -/ -/,/5/ -/ DM ; 1. O ,< /, 8+- + 5/ -/ +<;, ;/,//, -+/ + / - ;+5+/, -/ ;5/ 8+ -/ ;+<//, ;+-/, -/ DM 1 > -/ 39 / 6(@ +;, ?, / << +,@ /,;/<+5//@ +- ;/,//, -, +<;,. + ;/,/+ -/ ?, +<;, <>// ,< -/ 100 /5 << +,. A AI:2@ +55 <H/<- <5 ICA:!12@ 5+ ;/=+ /;/,,+ /<- //-< / / ,/ /<+ +, <+, + / ;+</<+,. O, 5/H/, /,+, -/ 5/--+ , , +-5/,+,. S+ ,/,-+-/ -+8,< -/ DM 1 ++ -/ 60 + 70. A ;,-+-/ -/<+ <5 + -+ -+ -/+@ ,/- 5+ /5 ;+<//, <5 -+8,< -/ DM +/, -, 10 +,. E5 /,5@ , +<;, , 5+<+-/, -/ +5-+-/ / ,+ ;/,/+ -/+ -+// - ; 1A. E5 <++, <5 DM 1@ /,/ ;,-+-/ ;++ + ;/,/+ -/ +<;, /5 90 -, <+,,. O +<; +:,+ /, ;/,// /5 -=-, 5+, /,@ ;<;+5// <5 =< - DM +/, -, ! +, -/ -+-/@ ,/- 5/H 5+<+- -+ -/+ /,,+ >++ /+. O +-/,<++,/ - <- 85< /5 ,/ 5/H -/,/5;/H , -=-, <5 =< -+ -/+ +<5+ -, 20 +, -/ -+-/@ / / ;/5+/
P8 35 ,935-C O, =/, -/ ;/;=-/:C &PEPC' ?5 ,- /5;/8+-, <5 5 =- -+ <+ Q@ ,/- 5 /+5/ ++ + <+,,><+ - ; -/ DM / + /,<H+ <+ -/ ++5/. A ;/,/+ -+ ,/</ /-8/+ -/ ,+ /, </+<+-+ <5 5/H </ 8=8+-@ / ,+ /5+ /<,+5// /+ / 5/+:-+ -/ 30 5,. A5 -,,@ , -/ ,+ /8/+ />// <5 + -,+8/5 -+ ,+ /-8/+@ + ;+,, / PEPC ,>/ /,,+ />/?<+. 49
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A8, +/, ,8//5 / + +,+ ,KH ,/+ ,><// ;++ <+,,><+ ;+<//@ / 5 /,- 5, / + +-`5< - PEPC &; -/ </ -/ 1@! 8]5'@ 5/-- + +/ H+@ ,/+ 5+, ,/,=/. E5 /,5@ + 5/--+ - PEPC 5,+:,/ 5 5 5+<+- -/ > -+ <+ Q / -// ,/ /+K+-+ <5 8/ 5,+ /<5/-+- ;/+ ADA@ 5+, /,/ <5 1 58 -/ 8<+8 E* 5+, ,5;/, / 8+5// /><+K. *+/, /,5+-, 5//, / 1@! 8]5 -/>/5 ;+<// <5 DM ; 1 / +<5+ <5 DM ; 2 &F8+ 1'.
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!2
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bCL9@ CbCL10@ CbCL11' / ,/ /<, TH1@ / ,/</+5 IFN:W@ ;+ ;/;/+- ;<, TH2 , /<+-, , /<-, ;/+, 5<+, CCL17 / CCL22@ 8+/, - /+8,@ + ;- -/ >+-/, - <5;/5/@ /5 +<;, ;,K+/, / /5 <<-+-/. A, <+, TH2 ,/</+5 IL:4@ IL:!@ IL:6@ IL:10 / IL:13@ / ?5 ;+;/ ,/ + ;- -+, <<+, TH1 / /,5+5 , ><, B + ;- -/ 58+, /,;/<=><+, &71:72'. A,,5@ +, 5<+, ;-/+5 / ;+;/ 5;+/ ; -/ /,;,+ ><=<+ ;/-5+/@ ,/ TH1 TH2 &70'. A ->//<+ /5 5+ + /,;,+ 5/ ;+/+5=+ -/ 5<+, /;/,,+, + ,;/>=</
N+ T@ + 5++ - >+- ><=< +8/ <5 <+, TH1@ >+/,8<+,@ ;/5+/+ ><=< -+@ -//5+ + +;;,/. D/>/, +, <+, T/8 /,+5 + H;/;- -+, <<+, TH1 / ;-/+5 /,+ /-, + ;+8?/,/ -+ T. N+ DG@ ;/-5= -/ <<+, TH2 >+/<, B. O +5/ -+ < +,,<+-+ + <5 + /,;,+ ; TH1 + TH2@ ,8/- / + DG ;,,+ // ->///, ;, -/ /,;,+ 5/. U5 ,; -/ /,;,+ TH@ -/5+- TH17@ +55 ;-/+ /,+ /- + ;+8?/,/ -+ DG. A, <+, TH17 -/,//5:,/ /5 /,;,+ , <<+, IL:23@ IL:6 / TGFQ 1 ; <+, -/-=<+, / ++8K+5 +, /,;,+, ; TH1 / TH2. C<-@ + DAIT /,+- -+ /+ // 5;, >+/, +5/+, / 5;, 8//,@ <5 5;<+ +/ + - -+ +5-+-/ /5 5 -=- /5 5+ ;;+. E5 +, ;+++,@ >+ +5/+ /,;/<=><@ + ;/,/+ -/ 8// -/ ,,+ +5/+ / 5 ->/// 8// -/ ,,+/, +5/+, / 8//, + - -+ +5-+-/ -++@ ;,,/5// /,+ -/,/5/ -/ /,+8+, -/ ;// /5 5+ -//5+-+ ;;+.
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REFERÊNCIAS #I#LIO&RÁFICAS 1' BERTOLO@ M+/ B+,. C,/, +,/ -+8,< / ++5/ -+ +/ /5+-/. R<. #+6. R/,58. @ S P+@ . 47@ . 3@ / 2007 . D,;=/ /5 hH;]]ZZZ.,</.],</.;H;n,<;m,<o+/p;-mS04(2: !0042007000300002p8m/p5m,g. A
N/+585BJ P/ D/K/,@ H 2001. D,;=/ /5 hH;]]ZZZ.;/-/K/,.8.];/o-/K/,]047.;->g A<+ - -+// 5/. A+K. #+6. C+358. @ S P+@ . 9!@ . 2@ A8. 2010 . D,;=/ /5 hH;]]ZZZ.,</.],</.;H;n ,<;m,<o+/p;-mS0066:7(2b201000120002!p8m/p5m,g. A/,;.]-/]/</<+,]N/</<+,2006:3.;->g A
