. - . -

[Overlap syndromes]H : ] / - ,] [ puzzle],] 25% . profil , . [1-3 ] 30-50% 15-20% . UCTD .Raynauds, /, , [/]. , [ anti-dsDNA, anti-Sm,ACA,]. : ] 3 , , ] . /overlap sndrome [ RF , RUPUS]. Sjogren , , , /, , , , .

[MCTD] Sharp 1971 , , , . MCTD -U1-RNP [ anti-dsDNA anti-Sm]. [ Alarcon-Segovia] : -U1RNP > 1:1600, : o ,, [ ],.Raynauds,.

: MCTD , /, . 2 4 [. : 35 , : 10 ]. : 1 : 15, . MHC , HLA-DR4 [DRB1*0401] HLA-DQ3 [DQB1*0301]. : MCTD 20-30 .Raynauds, ,/ [puffy hands] , [ ] , , , , , . ] => / , . , . [proximal] MCTD. CTD , , , , . MCTD, . ] => . / . . [ ] [ ,swan neck,]. . . , . MCTD . ] => 2/3 MCTD [ ] . MCTD /, ] => . . 85% . . ., , 12/, -. 25% , . , . ] => .Raynauds 75-100% . -

. [ ] 50-90% MCTD. , [ ] MCTD. [Peller et al,1985]. ] => . , . , , , []. . . MCTD, , . . . : , , , . ] => . 20% . / [ ,] . - , . ] => 10% MCTD. , ,, , , , , . . ] => Sharp 1972 MCTD . [] 50% . . -. ] => MCTD. : / , [ MCTD ],, , RF 70% -U1RNP 100% , -Sm -dsDNA [ Sharp dsDNA / Sm MCTD]. . 1/3 MCTD, . CPK

, . : MCTD . MCTD . , , , . [ / ] [ BAL, HR-CT, ]. ] [,,,] => .X [ < 20mg prednisone/day] . ] => ,, ,/ [ ] ] => [calcium channel blockers] [Bosestan]. , . ] => IV . ] => . => . => , . ] , . => , . => V . ] .Raynauds => [ , , ,], [ calcium channel blockers], [ iloprost] . ] => , . H2- [] PPIs . ] / . ] [1mg/kg/day prednisone] , per os, . : MCTD . 5/ 10/ 90% 80% [ ]. . MCTD .

Polymyositis Overlap syndromes . -Jo-1 [ histidylt.RNA synthetase], 15-20% , . : [100%], [50-75%] , [60-100%], .Raynauds. . [ , , ]. - . 50-70% -Jo-1 , 10-20% . . , . . -, , . t.RNA [ -Jo-1] .

Overlap syndrome SLE & Sjogrens,defined by anti-La/SSB La 1974 . [ RNA ] anti-La/SSB .Sjogrens. /Sjogrens overlap anti-La/ SSB , , .Raynaud, . 30% . , [30% ] Sjogrens. MCTD. anti-La/SSB overlap , .

Rhupus [overlap syndrome SLE & RA]H , . , overlap [ & ]. Rhupus . case reports , Rhupus [ ]. , -U1RNP, - [MCTD].

Scleroderma Overlap syndromes : => [ . CREST] 4% 17% . , 5% . 25% , . 30% , .CREST. 70% [ ] .Sjogrens. => . . [ ], , / /, . , , , , , - /. . 153 [Bohan et al,1977] 21% , V . [36%] . , 50% -U1RNP Alarcon-Segovias MCTD. [ -Ku , -Pm-Scl ].

V . MCTD.

[APS] KEY POINTS : / , [ 10 ] [ 10 ], . [ ] APS . [, , ] [ ,.Budd-Chiari, ], [ ,,-]. , APS - . coombs .Evans, , , [>], [ ], , , , , .Sneddons, , , ,. [ ] [ ]. APS . . aPLs [ 2-GP-1 ]. aPLs : , , 2- 1, . PS . - . : [ ], , . , , - , [1-3%, ]. [ 10-20%, 20-40%]. / . IgG , -

aPL . PS MHC [HLA-DQB]. aPL , . . : . aPL GPL & MPL units. : : , . Doppler , . , : 1. 10 [ ], 2. 34 ,, , 3. 10 , . : IgG / IgM , 6 , [ ELISA 2-GP1 ], , 6 ,. APS : APS , < 45 , , , / , , . aPLs [MS]. ] => [65%] / [35%] . . . , APS. , [ ]. - , -

[15% / APS , . - ]. [,, . APS .BuddChiari. aPL Addisons ].

[ C, S, ] APS . , . MRI , , . , , . aPL [8% ,18-40% < 50 ]. 1/5 aPLs . aPLs . , , [Lupus nephritis] . APS , , .

aPL , [ ,] , APS . . . ] [fetal loss] => APS , [ 10 ] 50% . aPL [ 1 ]. 2% aPL 0.2% , [screening test] , [, / , ,,]. aPL / . , . , . . APS . ] => 1. : , . , . APS . Coombs [ Evans], 2. , 3. , aPL , 4. / -

. MRI [ APS , MS ]. , 5. , [ aPL ], 6. [ ], [ - , , ], [ ] . .Sneddons, aPL , 7. Lidman-Sacks 1/3 APS . , . . 25% [ ]. . aPL , 8. , , aPL . aPL , 9. APS . APS : APS . aPL 1/3 . . ,, . . , . : , : [PLTs], / [ ], C,activated protein C resistance[ratio] Von Leiden, S, , & , , , ,,C3/C4, , [ anti-treponemal antibodies + VDRL], 2- 1.

, spiral CT- / / . aPLs APS . aPL, . [ IgG IgM]. VDRL, . . , - / o . : APS, . : , . 18% . C, S, , . [1% ]. , V [ V Leiden], 5% , C 10 . , , 2-3 . VIII , . [, , ,, , , ] [ ,,,,, ,, ] . [SLE,Behcet,Buergers disease, ,], [ ], . APS, , , [ ,,

,], [ , ,]. [ , Danaparoid Argatroban/Lepirudin IV], , , [DIC],. APS, , DIC aPL [ 60-80% HIV ] . grug-induced lupus aPLs , [ ]. aPLs [ ], [ ] : ] [ , , SERMs [ Evista], - , COX-2 ,]. ] aPL => IgG , [75-100 mg/day] . [Khamashta 2000] [INR : 1.5] aPL . [ , IV,]. aPL , . ] => , [warfarin] INR 3 4, [ ] . . [, , ] INR 2 3 / , [INR 3 4].

, per os [INR > 3], [ ] , . , [INR > 3] . [ , 1.5 2 ]. . [ illoprost] . ] aPL => aPL / , [75mg/ day]. , [75mg/day]. / [ ] 2 3 , [5000 10000 IU, ] [75mg/day]. , -D . , . , - [0.4 g/kg IV-IgG 4 , ]. APS , , 6 . ] => [100.000 150.000 PLTs] . [ < 50.000 PLTs] aPL . APS , , , -[IV-IgG]. APS . ] APS [70-100 mg/day]. , [Hughes 2001]. ] APS . ] APS [ 2-GP1].

[*] INR [>5] APS , => 1mg . 12h warfarin [ . ]. INR [>5] fresh frozen IV. : . , . . APS . IgM . [INR >3] , . aPLs : ] : IgG anti-2--1 , , , ] / , ] : / , [,, ], IV ,, ] , ] COX-2 [ ], ] : , ,, [ C S, factor V Leiden APC resistance, , ,].

STILL KEY POINTS : ,- [16-35 ]. [>39], , / , o , , , , . [ ]. . Still . , [ ]. 16 35 . : > 39 C, , RF[< 1/80] [< 1/100]. : 1] [ > 15.000 cells/mm3], 2] Stills, 3] , 4] / , 5] . : 70% . ,,, . . , . , . . . ] , [ > 39C, 2-4 ], . [ ] 24, , . . Still [ ]. 80% , . ] ,, , [ -

]. - [ ]. [85%] / [74%]. ,,,, [50%], [35%], [20%]. [ ] . .Still . 50% . . Ro . . / Still . - . , [50%], [20%], [10% - ]. [5-33% ] . ] Still : 85% . ,, , , [salmon pink]. . [ 15% ]. [ Koebners] . [- ] . . ] : . . . ] [, , ], , / . [ 10-15000 cells, , ] 30%, . /ARDS, , , . ] Still : , [ , , ], , [ , , , ], [, Sjogren, ] : . , [> 15.000 cells/mm3, 80% ], CRP,, . [ ]. [ ], .

[RF] , . [ > 1000 mg/dl, 50% > 4000 mg/dl] . , . : . Still . , [, ,TBC,], [,], [SLE, MCTD]. : [ ], [ ,, ], . ], . 10 50% DMARDs 1/3 . , : ] , ] / , ] , ] , ] . , , , , , [ , ], status epilepticus,. [5 90-95%]. : ] => 25% , . [100 mg/kg /day, 15-25 mg/dl], [100-200 mg/ day], . 3 . [ , , ]. [SGOT,SGPT,PT/INR,APTT,Ddimers,etc]. [ ] , . , [ ,,, ], [prednisone 0.5 to 1 mg/day ,

]. - [1gr/day,for 3 days] . 50% . . , . ] => DMARDs Still . , DMARDs , , , , . . [ ] . , ., [ ,,] . [ , ] , . - [IVIgG] , . Still TNF- , -TNF . 10 .

KEY POINTS : , . , . . /RF. - [ , , Feltys] . => ,, , [ , , , ]. , . , / . . => . , peak 40-60 . 1%. , 3 1. [ACR 1987] => [90% ]. 4 7 , . 1 4 6 . ] 1 , ] 3 : / 3 [ 14 : , ,,,,, ], ] : /, , , ] : / , ], ] : , ], ] RF [ ],

] : , . . => ., . , . . 10% . , , , , , . [40%] [20%], [20%] / [15%]. , , . / , . ACR , , .

=> ] [ ], ] [ ], 1 2 . . [ ,< 15 min], ,

2h, [ ]. . : ,,,, . . , , . , / . ,, , , . . H , . [ ]. / [ ], [ /bone to bone crepitus]. : [95%], [80-90%], [65-90%], [60-80%], [50-90%], [50-60%], & [50-80%], [40-50%],I [40-50%],[40-50%], [20-30%], . [ ]. . , [plateau] . / . : /, , . , [ ], , [ ] [ ] . [ . , Guyons canal syndrome ] , . , . , , /trigger finger . , -

. 3,4, 5 /. .H [ ] , . . : , buttonniere duckbill / . - [ .Raynaud, , / ,]. [ , , //] . , , . [ ] . . . , . . [] . / .

, , ,. : 17% . 10% , [1 ,2 ]. . , , /cock up hammer-toes, / valgus . -

, , . . [] . / [] . . , . . [ ] . ,, . : 50% 10-20% . , . . . . .[ 4 5 , ] , . . / . : [ ], . , . . , - . , 100 . Rotator cuff [ ] , [ ], , [50-100] . . . , ., .

: [ 30-50% - & ], , . , RF, [ ]. [ ], , [ 2/3 & 3/4], [ ]. [ 40-90% , ], [7-34% : Babinski, , , ,. ]. 1 4 . 1/2 [] . - : 25% , , . , . : [20%], . . . , / . , . , . , [ ]. . : [3-5%], 80% . [] . . . Bakers , [ . , ]. [ > 1000 mmHg] , , . Baker.

, . - : , , [ ]. , , . [ ], [, , ], CT. / . => - : RF, [], HLA-DR4, . : ,, , . . . Hodgkins, . . : : 20-35% [ ]. . [], , . , , , , /, , . . . [ ]. , , . [ ]. : , 12.5 /. , , , . , . . , . -. . - [ RF]

. - [lifetime risk 9:1] [lifetime risk 38:1] .A , [ ]. , . - , , , [] DMARDs , [ , , , ]. , . . - [ ]. , , . - [ : - , , , , . : , , . : ,/ . : , . : ,, . : , , , . : ,, , ,, , . : , .Sjogrens], , . 5% . , [ 3 4 ] C4 . , . [ ] [ ]. , . [ ] / .

: [ . Sjogrens - 35% ], , , [], , . [ , , - .

red eye [ ]. - . , , . [ ] , . , . [ ] , / scleromalacia perforans., .Sjogrens . [, ] . .Sjogrens. . Sjogrens, - [ , ]. [ non-Hodgkin ] Sjogrens . , SSA/Ro SSB/La .

: , [ ], , .- 75% . , .

. [, LDH], [ ], . - [ ].

, [ ] . . , . . . .Caplan . [ ]. [10%] , . . . . . , , , test . . [] [ ]. [] [NSIP] , [- /IPF /]. ,, , .

: , , , , . .

: 50% . . . [ ,, , ST ST / , , Ro 250ml ], [, ,, , - ].

[,,,, , , , QRS. ] ] . / . 80% 37% . ]. , [ ] , [ ].

: . [ Sjogrens] [ ] . [ , ] . . .Feltys 65% . . : . 110 , 40% . , [ ], AA- [5% , ]. , . . / : . - , 3 : 1-2 [ , , ]. step-off [ 4/5 & 5/6]. . 1-3 -

. Lhermittes [ / /, ] . , [ ], ,. [ Babinskis sign, Hoffmanns sign]. . /. . [ ], /Guyons canal syndrome, , , , . [ ], . , - . / [ ] . .[ , = ]. [ , , ]. . .

: Feltys: ,, . 1% , .To .Feltys , RF [95%], [ ] . ,/ [< 2000 cells/ mm3],,, [, ], ,, .. . Feltys ,, HLADR4 [ 95% ]. .Feltys [20 ] non-Hodgkin , [ ]. .

[ ] [< 2000/mm3]. . .Felty [ > 80%], RF [ > 90%], , C3/C4, , , , [ . Feltys : .Feltys , ]. [ ]. DMARDs [ , D, ,] . DMARDs . < 1000 /mm3 [G-CSF 2-5 mg/kg/day > 1500/ mm3. ]. G-CSF / . . . Large Granular Lymphocyte [LGL] syndrome - Feltys. ,, , [ CD-2,CD-3, CD-8,CD-16, CD-57 . , cells] 1/3 .Feltys .

: H [- ] . . . [ TNF,IL-1,IL-6, ODF/RANKL] - . [ ], [ , accociated , ], [ , ,] . [ ] [ ] . - . 1993, 12% , 6% [ ]. -

, , . : [ ], , [ & ]. . , CPK , / . . / [,, ]. => [amyloid A/AA] . , CRP , . , . , [ ] [ ], , , ]. -, , . . . : , . Feltys, . [28-38 / 100.000 /] [5 /100000 /]. . [80%] - B,C, G. - [> 80 ], , , , . , , . , DMARD . .

: ] , ] [ ] . [Drosos et al], : [70%] => . RF 85% , . , , . RF, . RF [- , , - ] . [ ] RF . [ACD] [IDA] . . [ ACD]. . / / . . - [ ,, Mayer ,] [ ,]. [ ], , . ACD . RFs . , . 15% . . . [ , , ,] / , [ / ]. CRP

. : , C3/C4 [ ], 30% [ anti-dsDNA,SSA/Ro,SSB/La,Sm,RNP ]. . , [5000 50000 /mm3, > 50%], , [ 40-60% ]. , . . anticyclic citrullinated peptide [anti-CCP] antikeratin/ [ 40-kDa filaggrin ] anti-perinuclear/APF [ periclear factor keratohyaline granules buccal mucosal cells] . , [ ] . antiCCP ELISA, [96-98%] . anti-CCP IgM-RFs, [Early] . anti-CCP 70% 33% . o RF [ C]. .

=> [ ], , , , , , RF, C3/C4/CH50 ,, ,, . : ] : [. & C,EBV,HIV,, 19], , , , / - ,. ] : , , CTD, Behcets, [ ],. ] : , , ] , , , .

] : , IV, , , [], , , , Lyme, , , -, RS3PE, Whipples, . => Short Bauer & Ragan [< 10%] . . 90% [ ]. 50% 10 , III IV, 30% 5 . [ ] , 10-15 [2-2.5 ]. => RF, [HAQ score > 1] , [ > 20 ], [ ], HLA-DR4, CRP, 2 , [ ]. [ ] => [42%] , [9%,], - [14%, 5 8 . non-Hodgkin -,. , . /-/ ], [4%, ],/ [10%, / - / /- ] : : ] [ ] , ] [ ], ] . . -

[Early RA] [ ] ACR . : ? - . 50% 80% early RA,. . Early RA , , , , . ? Early RA, [ > 12 ], RF, // , [], CRP. [US & MRI] . Early RA , - . MRI US, . ? . 5 . 40% 6 . MRI [ ] 4 . 6.5 .

. , , , . , / [ 1 5%]. , , , , . -

, [,,] , . - 11 1435 , , DMARDs. , DMARDs 53%. , . DMARDs , , NSAIDs. profil DMARDs NSAIDs. /Early , 3 . 2 , . . , , [ /HAQs], [ 10 cm], , , CRP. / [ ] . , , 36 . [Early] : [PISA Scoring system] . [ , , ,] . ACR , [Early] . [ MRI US ] . , [Early] Emery [1997] , PISA [Persistent Inflammatory Symmetrical Arthritis] scoring system. 6 -

[RF positive : 1 pt, HLA-DR1 or DR4 : 1 pt, CRP > 20 mg/L : 1 pt, Female sex : 1 pt, HAQ score > 4 and < 11 : 1 pt, HAQ score > 11 : 2 pts], PISA score 3, . Guidelines for the management of RA [ACR 2002] : ] [ 3 ] ,/baseline , , ] ,/ , DMARDs [ 3 ].O DMARD. / [ < 10mg/day ] ,] [ , , RF, < 30] HCQ + SSZ, ] [,, , RF, ] DMARDs. [ LEF] ,] 3 . [ DAS-28 > 1.2, ] . [ DAS-28 > 1.2, ] [ DAS-28 < 1.2 ] LEF, DMARD, TNF [ -TNFa DAS-28 > 5.1], ] , LEF, DMARD DMARD. [ , , ] . , [15-25 mg/week]. , . [ ,gel,] . [, ] [ : , , ,]. .Feltys DMARDs [ ,, ] [ granulocyte colony-stimulating factor], [ 50% ]. : ] , [,,,] ] [, ,DMARDs], ] [ : , -

: , : / , : ], ] [ 40 to 60 mg/day divired dose // /. / IV-IgG anti-TNFa ]

5-7.5 mg + MTX LEF - 3 * => DMARD DAS28 > 1.2

[Early RA] DMARDs - Baseline : 1. 2. [DAS-28] - Follow up 2-3

NAI

DAS28 > 5.1 DAS28 >3.2 & < 5.1 DAS28 < 3.2

* 2 DMARD. * anti-TNFa DAS28 > 5.1 [ > 4].

anti-TNFa anti-CD20 [Rituximab]

, , ,. , , , , / , [ / ], . [ ,,, ], , [ , ,], / . :

[NSAIDs] , , . /COX-1 & -2]. . , , , , ,. . , [ ], - [ ]. 50 . . , , . [15-20 mg/day prednizone, 1 3 ] DMARD. , , 40-60 mg/day prednizone [ ]. [.D, ,] . [7.5 mg/day] DMARD, DMARD, [Boers et al, 1997] [Kirwan et al,1995]. T [DMARDs] . , . DMARDs , . DMARD , , . DMARDs . [ 5 12 50% - , DMARDs 20%]. , , . , . TNF IL-1. FDA,

CD-20 -. . DMARD . DMARDs /early . step up [- ] DMARD , DMARD DMARD. DMARDs , step-down . /Combination Therapy. 50% 2 3 DMARDs. . , , . [ ] DMARDs : + , , + . HCQ [ ]. , . DMARDs :

: . , , IL-1. . [ ] , , . , . : 5 - . . , 2 [ 4,]. , [ ], [ 12 ], , , [ SLE -

, ], . : 5-aminoimidazole-carboxamine-ribocleotide transformase [AICAR] dihydrofolate reductase . , T- , [ IL-1 & IL-2]. Gold standard DMARDs. . , , , [ ], ,. PO [7.5-25mg] > 20mg/w . [ ]. NSAIDs . : [ ] . 20mg [ 3 100mg/day]. hydroorotate dehydrogenase . 2-4 [ ]. , , , , , . A: , DNA . IL-2 T-. [ 450] . , , , , , . . . Ca . , 3-5 mg/kg /day. [ & per os] : , per os [ ]. -1, , , , HLA-class II APC-, IL-1. [ , ,] [ ]. < 300 mg/L 10% .

> 300 mg/L. [ ], [ ]. D-: [,, , / , ,Myasthenia-gravis like syndrome,]. DPA .Goodpastures [ ]. : , DMARDs.H AZA 6 . 6- thioinosinic & thioguanylic acid . , T- [CD8] - , . [ ,,,,, ] DMARD. : - [Per Os IV ]. CTX . [ , ,, , ] DMARD. . , -, . : , . , , IFN- s. Early RA, DMARD FDA. .

, ., , DMARDs [DAS 28 > 5.1]. 2001, British Society for Rheumatology

anti-TNFa , [DAS 28 > 5.1], 2 DMARDs [ ], : 1] 6 [ 2 standard ], 2] < 6 [ 2 standard ] . : 1] , 2] , 3] [ TB , ,- . , , . Mantoux . - 300 mg/day 9 , , 12 ], 4] [ > 10 ].

30% , [ < 10 mg/day] DMARD [ : ]. [ anti-TNF ]. anti-TNF [ TNF , ], IL-1 [ ], - CD-20 - . 3 anti-TNF . . , Infliximab , Etanercept [ ], Adalimumab . , anti-TNF [Mantoux, ] - [ 5 mg/kg /day, 9 ] . anti-TNF . IL-1, Anakinra, , profil

- . , - , Rituximab. Infliximab [Remicade] : TNF. [ - 3 mg/kg - 0,2,6, 8 ] [ -/HACA ]. TTRACT , , , , IgM anti-dsDNA [ ] 16% , TBC-, [ ] , ,.\ Etanercept [Enbrel] : p-75 TNF. 50 mg / . , [ ]. . , [,,, ],. anti-dsDNA Enbrel, . Adalimumab [Humira] : TNF. 40 mg 14 . profil anti-TNF . Anakinra [Kineret] : IL-1 [IL-1Ra]. 100 IU / day IL-1 [ ]. . Rituximab [Mabthera] : CD-20 -, , , - , , 60% . Rituximab, [1000 mg IV 1 15 ], 24 [6 ]. profil . , -. . - [HACAs]. Stem-cells [SCT] : , .

[animal models] SCT , . Prosorba : , DMARDs . , . . . - . : ] - - [ IL-4,IL-10, IL-13], ] - - [ - -6/-8/-12, IL-8/-12/ -17, L-15, L-18],

=> . > 60 . [/ : 1/1]. [ ]. , [, ,] . RF , . [ RF]. .E, [ , T-, , , , ], , , -. , , . [,,], , . : ] [,,, ,] , ] 10 mg/day , ] 2

DMARDs , DMARDs [ , ] , ] , . - . RS3PE => , , , . [ ]. . [. = 70 ], [/ : 4/1]. , . [ ] . , , < 36 . .

KEY POINTS : , , stress [ ]. / . . [JRA] . > 6 < 16 [ ,,, , ]. 3 - , : - [1-4 . . ], - [> 4 . ], [ , Stills. ]. , , , , [SEA]. . , , , Henoch-Schonlein Kawasaki. . , , .Raynauds, , , , . / -. , . . . . => , -

, . insuline like growth factors . 1] . [ ] . , , . , , . 14 , . , , 4 . . , . 2] , . , [ ] . . 70%. , [ ] , . . . 50% , . 70% . [ ] [ ]. 3] , DEXA. . , : ,, D. , .

. , . , , .D , . 4] , . [ ] insulin growth factors [IGF-1]. . . h-GH. . IGF-1, , . . , . IGF-1 . L-6 , IL-6 IGF-1 . . VEGF [vascular endothelial frowth factor], . VEGF . o VEGF . 5] 1.4 IU/Kg/week , [ BMD]. . [h.GH] , . 6] [ ] . 30% . 40% . ,, .C, . TNF, IL-1 IL-6 . . 7] [ , ,

], [ , , , , ,] 40-60% . , . / : , : A] => , , , , . [, , ,,]. [,,, ]. ] => , , , , , . . , [ ,] [ ,]. , [], . , , / . , : , , Ewing, . 4-12 , , , , [ ] message . . . : ] => , , [ ,.Lyme],, [,

],, ] [ , , , ,,, ] => , [ /, , ],, [.Lyme,,], ,, , . < 5 , . [ ], , [ ,/Legg-Calve-Perthes disease,]. / . . [ , /S.Aureus/Moraxella/Enterobacteriaceae,,,] / ?

?

[, ,] ?

Overuse,

[JIA] ,

JIA [Still disease] [ SLE] /

[J] JIA . . , . , -

. 5-10% JIA RF, , . : JIA [ ]. [ ,4 , 10 , , , . 50% , 16 . ACR : ACR [JRA] 6 , 16 , [ , , , , , , , ]. JRA 6 [ ]. 3 : T JRA : [50% ]. - : ] [< 6 ] JRA [ ILAR JIA , ], ] [ > 8 ] JRA [,,]. 10-20% . Follow up 10 , 40% . T JRA [40%] : ILAR JIA RF positive RF negative . JRA [ Still] : ILAR JIA . ILAR : ILAR [International Association of Leaques for Rheumatology] [JIA] 6 , 16 . JIA. 7 : 1. [50%] => / : 1/5.X 4 . RF [ < 2%], 75-85% . 20% .

: [Persistent] JIA : 4 . [Extended] JIA : 4 6 . JIA : 1-5 , . [,, ]. [58% ] [24% ] [ 3 , 9 ]. [55%], [20%] [10%]. , . [14%] [5%] . 20% . 2 , 10% . 75% [ ]. 25% [ , ], 75% . JIA : [], [< 4 ], . [ , ,, ] , . JIA , . NSAIDs [ /]. , , DMARD . , , . [0.3-0.6 mg/kg/week]. , JIA , anti-TNFa [Etanercept,Infliximab]. . DMARDs . SSZ 1-2

[ , , CRP]. . [1 mg/kg/wk ] . -, . anti-TNFa . JIA 6 . 6 , 5 . 12 . JIA . 80% 15 . 2. RF positive [3-5%] => JIA [ > 5 6 ] , , , . , > 8 ,HLA-DR4 , . 3. RF negative [25%] => . : O RF negative : 40% JIA, [ 7/1] < 3 . . . [21% 42%] . RF . II [Polyarthritis with boggy synovitis] 20% JIA. , > 8 . , , , . [ > 40,]. RF . [Drypolyarthitis] 20% JIA.- , > 6 . , . . RF . IV [15% ,/ = 3/1, 8-9 ] JIA, -

[ > 4 ] . V [ERA]. RF-negative , HLA-B27, HLA B27 1 2 , IV JIA. JIA 4-8 NSAID. NSAID 6 . NSAID. NSAID, / , DMARDs [ , JIA, V JIA]. DMARDs, anti-TNFa [ Etanercept Infliximab]. JIA, , . 4. Still [10-15%] => / : 1/1. X [ > 38 C, ] [ , ],/ [salmon pink],- 3-5 mm, , . , JIA. . JIA, , . . US . [, , ] . . [,, ]. [ ] . . [,, ], [, , ], , , [,,, ], [ IGFs IL-6 , ], , , . [1% ] . JI , .

. [ > 75%] , , , [ 50% , ], [ [ 2-3 ], . peak 1 6 . [MAS] : JIA, [ Still], ,,,-, , [ , ]. [ ] [, ] . MAS [,,, NSAIDs]. , . . , MAS -, , , D-dimers, , . T- IFN TNFa . - . - [1gr/day for 3 days] / per os. Etanercept. , [] MAS. JIA : CRP,- ,, , [ ], , [soluble TNFa receptor,IL-6] Von Willebrand,. RF . JIA NSAIDs [ ]. NSAIDs 6 . NSAID . 6 . . per os,0.5-1 mg/day . -

6. , IV - [30 mg/kg/day maximum 1gr/day for 3 days]. JIA, . DMARDs . JIA. . anti-TNFa . [ ] JIA / . [IV-IgG] [ , ] , . , . : JIA Still, [ 2-3 ], [ - ], . 30% , . 60% 10 . : 8 , [], 6 , 15 . 5. H [2-15%] => 16 . , : , pitting , 1 . 6 HLA B27 , , [ERA], , Reiters, RF, . - -, . . JIA. 6. [Enthesitis-related arthritis / ERE] => ,

: / , HLA B27, > 8 , [, ERE, , , ] 1 . [ 1 ], RF, . Enthesitis-related arthritis, [SEA], , HLA B27 . ERE, [ 10/1 3/1]. 60% . , [ ]. - [ ] 40% , 75% , Enthesitis-related arthritis, , .Reiter, . 7. => [ > 6 ], , . . : [,, Lyme, ], [ , , ], - [, ,], [ , , , MCTD, .Behcet,] , [.Kawasaki, Henoch-Schonlein], [ ], [, ,, ], [ IV ] , [ , Legg-Perthes disease,]. . JIA LDH , , [scanning , / ]. : , . / .

. : NSAIDs [ .Reyes], [ ], [ JIA]. DMARDs, [10mg/m2 , 1mg/day] , . DMARDs [ ]. , Etanercept - . IVIG. , , . : 30% 10 , 30-55% 6 , [ / ] 54% , 45% 28% . 14 . [ ] . 10 85% , 15% [ 10% ]

N , . 4 : ] , ] , ] , ] . , , [SEA]. , ILAR [ERE] , - JIA. [ ] -

. 2-10 100.000 , 2-12 100.000 , => . 16 . , , / 6 1, HLA-B27 82-95%. . . . , . / [5-10% ]. [ ]. scanning / . CT . RF . . . , . => . [ ]. , , . => , HLA-B27 [ .Crohn ] . . - [ , , ,,-,, ,,] [ ]

. . , , , , . : . 5-10/ 100.000 . , . [4.5 : 1], . [ ], [ , ]. -Sm . ACR . 4 11 , . [ 30% ] , [, ,], . , / , , . 2/3 . , . . , , , . [50%], . 18 . Raynaud . , . [ ,,-, , , ]. / . , [.Cushing, ,,,,,-

]. [ IV , per os] . . [MCTD] : MCTD / RF . MCTD [ ] : [APL] [ 1/3] . APL , , , , . APL per os . , . per os . , . : : . , .CREST. . [ ] . , . , . . . .Patty-Romberg , [ , ], . [ ] . , , . [overlap]. . SSc anti-Scl-

70 . SSc. D-, , . HENOCH SCHONLEIN : [ ]. A : Kawasaki . , Henoch-Schonlein.H akayasu . Wegener .

Sjogrens [SS]KEY POINTS : . Ro/SSA La/SSB . .Sjogrens , , , , [ ], , .Raynaud [ ], , [,,] . .Sjogrens - . - , .Raynaud, . B- ,, C4, [ ] . .Sjogrens [ , , , , , ,] . Sjogrens [ , ], . : , [ .Sjogrens], [ .Sjogrens ,,, , ,, ,, , ] [5%] -. , , . : ] C4, ] [ ], ] , ] . : .Sjogrens [ : = 9 : 1 ] 4 5 . . . .Sjogrens 0.5 1% [ ].

1 2 . . 1 [] 5 [,] . : [ , ]. 3 6 , / 4 [ anti-Ro anti-La ] 6 . ] => : , 3 ; - ; - 3 /24 ; ] => : 3 ; - ; - [ ] ; ] => : 1] Rose Bengal score [ 4 van Bjisterveld scoring system], ] Schirmer-I test [5 mm, 5 ] ] => : 1] , 2] , 3] [ < 1.5 ml in 15 minutes. ] => /focus [ 50 ] 4 mm2 [ ] ] => : 1] Anti-Ro/SSA Anti-La/SSB , 2] /, 3] /RF. [*] : ,AIDS,, . : .Sjogren [] []. .Sjogren . 8-10 . : [45%],[45%], [24%],[5%],/[10%],/ [28%], .Raynaud [21%], [1.5%], [1.5%]. ] => . , , , , . ,,,

, . 2/3 Sjogrens, .Sjogrens . , . , . , : 1] => [ Sjogren, Lashley ]. , [,,, , ] , 2] => . Sjogren s . . , . [ & Talal,1989] . Vitali ei al 1988, , ] /Tc 99 => [60 IV , . Sjogren ]. , , ] => . ] => .Sjogren.H [/bulbar ], , / ,/ ,,. [ ] , . , , , . / . Schirmers test [ 30mm , 5 min . 5 mm ]. . rose Bengal. H rose Bengal [ ] rose Bengal, -

, . rose bengal, lissamine green. . / fluoroscein film, .Sjogrens . [] ] [70%] => , , [ Jacoubs]. , [ ]. ] Raynaud [35%] => /. .Sjogren . Raynaud / , / . . ] => . , . - - , , . .Sjogrens , . . 7% .Sjogrens. ] => [ ]. .Sjogrens , 50% . / / . .Sjogrens. , . Sjogrens [ .Sjogrens ]. : , [ Ro ] ] => , , . . ., Sjogren , .12,

. / . , 25% .Sjogrens. ] => [1994,Skopouli et al] 7% Sjogren [] 5% . , [ , ] . .Sjogrens [ 50%, 10% ] ] [10%] => .Sjogrens. , . / [ ]. , . , , . , .Fanconi. . [ ] .Sjogren [ et al,1978]. . ] [5%] => . .Sjogrens : [ , ], , . // // .Sjogrens . .Sjogrens , . , RF,-Ro/SSA , . [ - ], [ ] ] => .Sjogrens [ vasa nervorum ]. [ .] . . Sjogrens [, ,, , ,, ,] , .Sjogrens .

] => [/ CPK]. [ ] .Sjogrens [1% ]. iv . ] => [ .Sjogren TSH]. . Sjogrens [ - ,, CD4 T-cells , -. ]. ] => .Sjogrens 44 , // . B- IgM- , . H Non-Hodgkin . Sjogrens 4.3%. 7.5 . .Sjogrens , , , , [ ], C4 [Tzioufas 1996 & Skopouli 2000]. . .Sjogrens - /Non-Hodgkin . marginal zone B-cell MALT [mucosa-associated lymphoid tissue] monocytoid B-cell . NH .Sjogrens follicle center large B-cell . 60% Sjogrens , [low grade] . , [ ] . [low-grade] [high grade] . large B-cell . O . ,, [ ], . , , . .Sjogrens - [, ,-]. , RF .

SJOGRENS => .Sjogrens 1939 Henrik Sjogren. , , , , , . .Sjogrens 5%, 20% / . .Sjogrens . .Sjogrens , . .Sjogren .Sjogrens . .Sjogrens , . 20% . 20% . . 44 , 38% , 22% .Sjogren. => / [21%] , [6%] [2%] . 70% , CRP [ .Sjogrens ]. [70-80%] .Sjogrens. [RFs,ANA,anti-Ro/SSA,anti-La/SSB,,anti muscarin receptor M3, -fordrin,] . .Sjogrens [ 90% ], RF [60%], / [6%]. -Ro/SSA -La/SSB Elisa 90 85% . anti-Ro/La , , , , . .Sjogrens - [28%] [ ] . . Sjogrens [Tzioufas et al,1996]. : - / [ - ]. C [ ]

.Sjogren. .Sjogren, . - , anti-Ro/SSA anti-La/SSB . .Sjogrens [ II,IV,V], , HIV-. : Sjogrens.Box 1 : , , , [15 mg/day] [48 mg/day] , : NaHCO3 & KHCO3

: .

: Ursodeoxycholic acid [10-15 mg/day] -

Sjogrens

, : [200 mg/day] Raynaud : [15 mg/d], ,

[ ]

+ Box -1

[ +/-]

] .Sjogrens : - / . ] Sjogrens => : , 30 , air contitions, , // . [ ] : , [ ]

, , , Bromhexine [48 mg/day, /BISOLVON]. / , 30% [ 50% ]. . /SALAGEN [5 mg x 3/24h] /cevimeline [EVOXAC 30mg tabl], / . cevimeline/EVOXAC 3 [ 2 Evoxac ]. Shirmer II test [ ] . ,, -blockers . . gel . .Sjogrens . , [500 mg x 4/24h] . . , . ] Sjogrens => : 1] / => [200 mg/day], , IgG anti-La/SSB, . Sjogren [ ,], 2] Raynaud => [15 mg/day], 3] => , [ ], 4] => NaHCO3 & KHCO3 [1-2 mEq/kg/day] . , 5] => [0.5-1 mg/kg per day] / , 6] => , [0.5-1 mg/kg per day] / , 7] => Ursodeoxycholic acid [10-15 mg/ kg per day, /URSOFALK .Sjogrens , , . , . CHOP [Cyclophosphamide,Doxorubicin,Vincristine,Prednisone] .

DILS : Sjogrens HIV . ,, , , [] . , , , , , ,, , . DILS .Sjogrens CD8 T- [ Sjogrens CD4]. DILS Ro/SSA La/SSB . HIV .DILS Kaposi, B- non-Hodgkins .

KEY POINTS : . Raynaud, , , , [ ] [ ] . . . => [, ], , , , . sclero // /sclero. [ / / ], /Linear [ , - ,en coup de sabre] [ ,- Bushke, , ,] => [ : , , -] => ] /proximal [ . , , /, ]. => ] [ ], ] [ ], ] [ ]. . [SSc sine scleroderma,5% ] CREST , . .Raynaud SSc, - SSc / SSc- .

=> : ] [limited SSc] => , , / [ ], . [-]. .Raynaud 1 10 , . ,, [ ]. [ antitopoisomerase - 1] [ ] . .CREST : ,.Raynauds, ,, . profil [ACA]. [60%] SSc . , 10/ 70%. Pre-Scleroderma / limited SSc : Raynaud, , [ ,- -1,-RNA /], . Pre-Scleroderma limited SSc. . ] [diffused SSc] => [ , / /, , , ]. , < 1 .Raynaud [,,,]. profil / [ DNA- 1, Scl-70] - [ACA]. - [ ] , , . - 2 3 , / . / , . / , , -

. . 30% SSc , , 10/ 40% 60%. ] [SSc sine scleroderma] : [< 2%] [.Raynaud] [, , ]. . ] Overlap [ + ] => , , [0.002%], , . 40000-50000 /, / 3 4 SSs-like . , . , 35-65 , [ ] 7-12 1. => SSc .Raynauds, , . . , [ ] paffiness / . , , , , . Raynaud A / Tendon friction rubs Esophageal hypomotility /Renal crisis DIFFUSED-SSC 100% 30% 5% 85% 80% 65% 20% 75% 35% ,, [] / -

[ , ] stress. [3% 10% - 20% ],- [3:1]. , - shunts , / pallor /cyanosis . . 10 15 min . [ ] / . . 3 [,, ] .Raynaud. ., ,, / . . .Raynaud . . Raynaud : [ ,,/, , , Sjogrens], [,, b-blockers,vinblastine & bleomycin, , ], [ ], [ ,, , / .Burger], [-,,], [,- ,,]. [ ] 20 , .Raynaud . .Raynaud 15-25 , . , , , , , , anti-Scl-70, / . SSc, [/ / ] , [ , ], . SSc , SSc . SSc . Raynaud]. 90% SSc Raynaud

[] / ,, [ , , ,] . .Raynaud , . SSc .Raynauds, , . Raynaud, => ] /anti-centromere anti-Scl-70, ] , ] , ] / / [Paffy hands],] [ ,], [ ], , ,. Raynaud . [ ,,, ,] . .Raynaud [ , . - -, calcium channel blockers. 20 3 /24 , ] [ ]. , . PGE1 [alprostadil] PGI2 [i.e, epoprostenol,illoprost] 6-8 3 5 . , . micro-arteriolysis [ ] . , [Bosentan/Tracleel] SSc .Raynaud. RAPIDS, . => , . Rodnan system. 0 [ ],1 [ -

],2 [ , ] 3 [ / hide-bound]. 21 [, ,,, , , , , , , , , ] maximum score 60. : ] , , , . [puffyness] . .Raynaud. , . [ ] , , // / . , , . [ - ] , [ ]. [- & -] , -, ] , , . , 1-3 , ] . ,, [ ] . [ ]. [ ] . . . , [ ] . , . [ ], , . SSc. , .

,,, ,, 1mm cm. [ , probenecid, warfarin] . - . , . , / . "/mat" - 2-7 mm, /// . .CREST [ SSc, ]. . . Laser . / , / , , , . [ ] . [ ], per os . - . .Raynaud Bosentan [Tracleer]. => [,] . [ ], . SSc, .,- , . SSc , 3 . [2 3 ] - [ ] / , . . .Raynaud . ,, [Tendon friction rubs]. SSc , .

, / . , . [ COX-2 ], [,] . , [ prednisone < 10 mg/day] . SSc . , M// . . . , CPK . / . . , . SSc - [20% CPK . . ], [CPK 2]. [ -D,]. . SSc. . . => , , [70% ] , SSc. [ 25% , ] HLA-DR3/DRw 52, -, anti-Scl-70 [ --1]. [ ], 10 % .CREST. SSc [ACA] fibrillarin [anti-U3RNP] . -

, . : SSc . [ ] . [NSIP]. , , , . ,, , . , . , screening test [ ]. , . CO [DLCO] 70% SSc . DLCO . [ FVC]. 2 , SSc. [HR-CT] . , - . / , - . -. HRCT , - . - . / BAL, . HRCT, BAL HRCT BAL , [ > 50% HRCT] . BAL . , , BAL . DTPA [ DTPA SSc. , ]. HR-CT -

, , . SSc NSIP [ ], IPF [ ] UIP [ ]. . [.] O . [IDF,: ussual IP] - HRCT. .Sjogrens,/,MTCD,PA. 2 IDF. [NSIP] AIDS. HRCT . IDF. ? IDF ? . 3 [] , . . ARDS HRCT. 4 K [COP] . , . ,,. . 5 . [LIP] AIDS, - , .Sjogrens [ 1% , ]. : ] , ] [ 3-5 ], ] [ ], ] , ] [ ] 1

: , [ DLCO],HRCT, , DTPA.To BAL . 1 / . . HRCT , [20mg 30mg ] [600-800 mg/m2] 1-2 mg/kg . 6 . 6 HRCT. [ 10% ], 2 . HRCT , DTPA , . DTPA-scan , BAL [ BAL]. 3 .

10mg . IFN- . : , . /PAP [ > 25 mmHg > 30mgHg ], [< 15 mmHg] /PAWP. [ > 25 & < 45], [ > 45 & < 65], [ > 65]. . 60% 2 . [ & ] . [ III & IV] , , , , , , . ,, ,, S1 S3, . . Echo Doppler [ & /VTR : 36-50 peak VTR > m/sec], [ DLCO < 50% / FVC]., , gated cardiac MRI stress-Echo, . . [ spirar CT- , / , ]. , - . 2 [ - & -] - , , . [ ] . 3 : ] , ] , ] [/ 2// => , / TGF- => ] SSc [ SSc ]. : ] , ] , ] [SLE,SSc,APS,MCTD,DM], HIV , , , ,]

[PAWP > 15 mmHg], ] [ - , ,, ]. WHO 4 : ] [ ], ] [ / , ], ] [ / ], ] IV [ ].

class III or IV : oral anticoagulants +? Diuretics +? O2 ??? NAI Oral CCBs ??? NAI OXI ??? Continue oral CCBs Artioseptostomy +? Lung Transplant OR Combined Pharmacology +? PDES Inhibitors [sildenafil] NYHA Class III OXI NYHA Class IV

BosentanOR

[iloprost,epoprostenol,etc]

Prostanoid Analoque

[iloprost,epoprostenol,etc] OR

Prostanoid Analoque BosentanOR

IV Iloprost

[ . IV [ ] [ ] . [2 < 90 %] 2 [ 2 L/ min ] . /CCBs , . 85% SSc CCBs , [Illoprost,epoprostenol] [ , , ] . IV [sestan/ Tracleer 62.5mg x 2/day 4 125mg x 2 /day].-

. . , . [ ], [ SSc. overlap / / , NSAIDs ],o [ , / Ro ], [], [ , ], drug-induced . => , . . SSc [ , NSAIDs dcSSc, ], [ ] [ - ], , [] , [30% dc-SSc], .Raynaud. , . [ /patchy] SSc. / - [ .Raynaud]. Raynaud , , .Raynaud . MRI spiral-CT. o U/S , . , 30-40% dcSSc. , -

, .. SSc , , [ ] . L- , . C . , , . SSc , [bypass] . => SSc .Raynaud. 90% [90%]. , . . Auerbach [ /vasa nervorum] . , . , , , . , , . SSc [ 2/3 ] [ ]. . . , . , . [ ] . , [], , Barret . .

2/3 , . 1/3 [ ]. , , . ,, , Barret's, , SSc . , , , , . - ,5 6 / 24, 3 4 , . [ ] /PPIs [ omeprazole].O PPIs. [ ] , , . /Primperan. , NSAIDs, [watermelon stomach] . . [ , ,] . . , ,, . , [,6, 12, 25- D3], ,, test D. , . . , [ ] [ ]. SSc , . . -

. . [ ].- . [ 2 ] [ ,,,-,] . , [ 30 ], /Sandostatin [ ]. / [ ] 10 , . , , [ ]. [ /Imodium, ], . - levine . - . , [ , ]. [ , ] , . lc-SSc. : , [ ]. SSc . SSc renal crisis [ > 160/ 90 mmHg ], grade III [" " / " " ] grade IV [ ] [ 1 ] - . [ , ], , - . 80% 5 SSc.

, , . . [2 /]. : , , 3 mg/dl . : , [- ], [> 20 mg/day], , //, -RNA . O ,, - , . . 6 dc-SSc 5 , . - . - dc-SSc , . , > 20 mg/ day, . [ ] , , [ ,- ], [ / ]. : , [ ] , . . . - . [ ]. . [-] . - [ ]. 20 mmHg 48 80-

90 mmHg. IV [ ] SSc renal crisis. . , , - . , . , - , .. . 50% [ -] , 6 18 . 24 , . - [ACE- inhibitors] , 1 15% 75% . , . - , 1-7 [ - ]. -, : ] : , [ . - vasa nervorum. ], [ 30% , ], [ / . -, , vasa nervorum], ] : [ 3% lc-SSc], [], [ lc-SSc], ] [ , . ], ] [ + 20% , . 30% SSc ], [ 20-40% ], ] [ 50% , ], ] /sicca [ .Sjogrens].

: , . , . : ] /disease-modifying, ] [ -/ organ- specific] . , - . / , . : SSc, ,, . , . , , . D- [ . ], , IFN-, ketanserin , photophoresis/extracorporeal photochemotherapy] , . : placebo , [ ] placebo. IFN- - . [ ] placebo IFN-. IFN- . placebo, 24 , 25 g/kg/day /relaxin [ , ] 3 5 , . placebo. [, ,anti TGF- ,,,] . SSc . .

SSc

IV [illoprost] Bosentan PO [ Ca] IV [illoprost]

.Raynaud

: ,,D- [250 mg/day] IFN

dcSSc & lcSSc

: +

PPIs [ Primperan,Cisapride, -,] . /IV/

-, ,. - ACEI

[20-30 mg/day maximum] 6 [0.5-1 gr/m2 IV , 1-2 gr/d per os]

ACEI .

SSc. . [ & -] : [ ], [ PGI2], [ ], [ ], [ ]. 1 ,SSc, overlap . SSc BAL, [ lc-SSc ]. Tracleer[Bosentan] SSc. SSc, Tracleer [ BUILD 2 ]. ,

, - Tracleer [Bosentan] . : case reports , , - SSc. - . - SSc. - , [ 3 -]. - . , , . [ ].

Scleroderma-Like Disorders 1] [EMS] : 1989 . . L- . CDC [Centers of Disease Control] , => 1] > 10%, 2] , 3] / . EMS ,,, , Diffuse Fasciitis with eosinophilia. , /scleroderma-like,,, , . , . EMS. ...] / [ 3-6 ,, . 44% 14 , 82% 36 ], ] , ] / [maculopapular erythematous skin rashes], ] [ .

50% . / 43-90% EMS], ] [ , / . : , , , , ],] , ] , ] , ] [ . , . , , ], 10] . => ] [ EMS Raynaud, ,,tendon friction rubs], 2] /DFE [ EMS , . EMS , DFE . EMS. EF] EMS => ] L-tryptophan , 2] EMS, 3] [ , , , , D-]. 2] /TOS 1981 . TOS , . , .Raynaud, , . TOS EMS, / - TGF- & PDGF . TOS, . 3] /DFE Shulmans syndrome : 1974 [ ]. [ ] . scleroderma-like syndromes, DFE Raynaud, , , -

, , [ ]. /DFE 30-40 , 50% . : : , [ - , ], . DFE [ ], SSc , . , . , . , CPK . , . . DFE. , , , , - , . [ , , ]. ,, . , [ , ] . : DFE : . 50% [ , 85% ], 15% . . , , , D-, . / . 4] /Scleroderma-like : ] /scleredema -

- . , [ ] .Raynaud. - , ] SSc-like , -,, , , .Werners, -, bleomycin, , POEMS [= ,,,, ,SSc- like ]

Enviroment-Accociated Disorders SSc . . , SSc . [ trchlorethylene] SSc . - , , , . SSc-like syndrome . [ SSc, , MDCT, , .Sjogrens,] , . [ ACR].

Localized Scleroderma [ , ]. , . . . : [ ], [linear] , en coup de saber [ ] . . : , ,

[- ] . ,, , [ ]. [ ] . . [ < 3 ], [ - - ] . : . . 5% .Raynaud , . , 5 . D PUVA, . [< 15mg/day] . : [ , , ], . . - - . MRI [ ]. . En coup de sabre/ : , / . .

KEY POINTS : . ACR , . , 3 . [ ,,], [,]. - , [] . [anti-dsDNA,sm,anti-ribosome P], [ anti-ribosomal P ], [ anti-dsDNA ]. , , , , , , , . => . , peak 15 40 . 8 1. 1 2000 [ , , - ]. [ / 2 1]. , . [ACR] => 11 , 4 , . : 1] E : , , , . 2] : . . 3] : [ ]

4] : [ ] 5] : - , . 6] : ] [ ],/ ] [ ] 7] / : ] [ 500mg/day 3+ ],/ ] [ ,, ] 8] / : ] [ // ] / ] [ // ] 9] : ] , / ] [ 4000/mm3, ], / ] [ 1500/mm3, ], / ] [ 100000/mm3, ] 10] : ] Anti-DNA ,/ ] anti-Sm ,/ ] [ IgM IgG ,/ test ,/ 6 ]. 11] [] => [ Lupus-like syndrome] , . [ ] . ACR. , anti-dsDNA , , . => 80-90% .O : , 30-60% . [ ] [ -], , . . , - .

, . , , [SCLE] 7-27% anti-SSA/Ro . ,, - [, - , - , . ] [ ] . . [DLE] 15-30% . [ 2-10% ]. ,, . . . [ ] . , / [tumid lupus] . [Lupus profundus]. - [ ]. / [ Gottrons ] [ ], [ , ], . , . [ Lupus frizz] H . , , / -, , splinter . 5% .

.Raynaud [ ] 30% . [ ,,] [ , ] - . - [lupus band test]. , . [ Ig C3 ]. : [ ] + [, ], [< 10mg/day] . Lupus profundus . [25-50 mg/day] [ , ]. . . => [75-100% ] . [ ] [,, , ]. . , [ ], . . 24h . , . [5-10%] [ ,, swan neck,hitchhikers thump, Jaccoud] [ ,,] Jaccouds [ Jaccouds MRI]. /early . [ , test /, 2000 / mm3 , ]. [ , ] . [ ].

5% [ ], [ ], . [ 5-10% , , , , ]. [50%], . , ,.Raynaud, -. [ 400mg/day 3-4 , 200mg/day 3-4 , 200 mg/day /]. [< 10mg/day] / [?]. , , , LDL . - placebo 2.5 [ ,, ] . follow-up [ ] . => , , ./ 15% . , / /. / . [Lupus Nephritis] => 50-75% . [ ,-]. , , [ > 500 mg /24h dipstick 2+] / .H WHO . / [ ]. [, IV] . dipstick . 24

dipstick 1+ [ : C3/C4 anti-dsDNA]. [] [ ] [ ]. , / . , . . / / . US , . => . 500mg/day , 500mg2gr [ ]. . anti-dsDNA [C3,C4,CH50] , [ ]. anti-ds DNA , . , anti-dsDNA . / . [ ] , . C3 & C4 [ ] anti C1q [ ] . => , . , . -

. , , , - . WHO , [, ] [, ] . , . , . [ 2% ] . . WHO => WHO 6 . , , , , , , ,. , WHO . [ ] [ ]. /, 24h < 200mg [/], /, /,anti-dsDNA: ,C3/C4: /. [< 10%]. I . [ ] : 10-20% , . , [], [] . , [ ], . IgG [], IgM,IgA,C3 C1q. . . [ < 1 gr/day]. . , [ ds-DNA, C3] .

[5 > 90%]. , [ IV]. [ ] . [ ] : , . 5 90%, 70% IV. IV - / - . 1/3 , IV. 50% / < 50% . . ,, . ,, , [ wire loops , ], [crescents] . - , . - . : [ ], 24h [500-3500 mg. 1/3 .], [/ ], [/ /], anti-dsDNA [ ], C3/C4 []. WHO [ ], [ ], C [ ]. V [ ] : . > 50% . , , . [] . - [wire loops], - , , . , , 2% . LE- , [ ]. [ , , ] IV [ V].

- IV . [full house pattern] [IgG,IgM,IgA] [C3,C1q] , -,- - . [ ]. , - . IV [ ,, ], [ ds-DNA, C3/C4] , [,,], [10003500 mg/day ]. WHO V [ ],V [ ],VC [ ], VD [ ]. V [ ] : [8-25% ] - . VA [ ] , [IgG C3], [spikes] . VA . [ > 3000 mg/day ], . V , . , . LASER, IgG C3 IgG, C3 IgG. VB, [ IgM] . VC, [ ] . VD, [ IV] . VD VC [- GN] , , . , . , , - , .

. H , . VI [ ] : . , , IV . , . , . VI , . [Activity intex] [Chronicity index] => . Chronicity index . Chronicity index. Activity index . 0-3 : [max : 24 pts] => , /, , ,/ , . [max : 12 pts] => , , , . => [ ], , , [ V WHO] [ V WHO] . [ V WHO] [ ], [ < 4], , IV [ , ] [ > 4], . [ > 2 ] 6-12 / > 1gr/24h [ + Wegener] [ V WHO]

, => 15% 10 . 3% / , . . 10% , . . [ ] . , 6 12 . , . => , [prendisone 1 mg/Kg/day, 60-80 mg/day, 3 ]. , 6-8 > 1 gm/day, WHO . [cyclophosphamide: oral 1-2 mg /kgr/day IV 0.5-1 gr/m2, 2.5mg/kg/day] [prendisone 0.5 mg/kgr/ day] , IV [0.750 1 mg/m2 , 6 ] 2 . [1-2 gr/day,per os] . [.: 10 ]. IV , [7.5-15 mg/day ] [2-3 mg/kg/day] [1gr x2/ day]. [ , < 1.5 gr/day], [0.5 mg/kg/day] [2-3 mg/kg/day]. , . - [ ,A-MEA, -blocker] . IV - [1gr/day,for 3 days] standard

GN : [ < 1.5 gr/day, , / < 50] [ ,,-blockers,] GN : [ > 1.5 gr/day, , / > 50]

0.5 mg/kg/day , [2-3 mg/kg/day].

?

0.5 mg/kg/day , ] IV [0.5-1 gr/m2 6 1 / 3 2 ] ] [1-2 gr/d] * GN IV [1 gr/day for 3 days]

[

?

=> =>

[ ] Rituximab [anti-CD20] stem cells.

[ & IV] /MMF + IV , + . F , [,,] , [15% 10% ] . F . . [ ], [0.5 mg/kg/day] per os [0.5-1 gr/m2 IV, 6 ] 6 .

=> 1575% . . [ ] , , , [ ] , ACR 1999, . 12 7 , SLE. : , [, , , , ], [], [, , , , ], [ ], [ ], [ ], [ ], , , [,, ], . : Guillain-Barre [ - ], , [ ], [], , gravis [ ], [ ]. , . [ , , , - , ] . [ , , , , , ] . . 80% [ ]. [ ]. ,

. [IFN-a & L-6] . . , IgG [ ]. , - [anti-P] [ ]. [ ]. MRI [ CT] . , . [ ] . US . , , , [,,, ], , , [,,V-IG, , ], ,. / => : . : , , , IgG [ , band IgG],- [ ], . 30% , ]. : [ ]. [,,-] , II ] : [ ], anti-Sm, , P [ ] . anti-ds DNA C3/C4 ]. .

/CT [ , , ,]. /MRI CT . 20-80% CT, MRI. MRI 2 - . , , [ , , ]. . [ ] . [ 2 ] . , corpus collosum 1 , . MRI . , MRI , RI ]. /MRS, -31, [ ]. /, [ ] . CT /SPECT, . 90% [ 33%]. => 19 . , stress , , , . : 20% . ,

, [ , , ], [,, ], , -. , - 24 [ ] . ACR, [ ], , [ / , ]. : 5% . . 5 , , . [ ], [ ]. . : [ 3% ] . , . [> 5 /mm3], . MRI. . . , / . : , , , .Parkinson . . , . : [15% ] . . [ ]. . . , -

, , , . : [30% ]. , . .Raynaud , . . : . ,, , [ ] . . : Lupoid sclerosis , . . : 7% . , . III, VI, VII [ ]. . : 10-20% . , . . ,, .Guillain Barre . , . . : [ ] . gravis: gravis . [ 75% ] . => . , [ ]. ] [ ,, , ] [,,,,]

] [ ] , ] , , [1mg/kg , ] ,IV [1gr/day, 1-3 ]. , [, per os IV ]. 13 , [per os 6 ] . , . 6 IV [0.75-1 gr/m2] . , CD20 [Rituximab]. ] [ ] Warfarin. per os , INR>3, ]. => , [25% ]. ] [ //// . . . [ ST aVR V1 , ST ], . . [ 30.000/mm3, . /LE-cells. ]. , , . , . . [ ] , ,20-40mg/ day 2-4 5-10 mg/day . [ ], 2-3 mg/kg/day [ ]

] [1-3% ]. , , , , [ PR ], , / . [ ]. ] [ ] . [ ,, ,, Libman-Sacks].H Libman-Sacks [ ] , 1-4 mm, . . Libman-Sacks 50% , . Libman-Sacks aPL , . - / . . , [ ]. , . SLE. LIDMAN - SACKS +/+ +/ CRP aPL : Lidman-Sacks [ / ] . , , . , . . , [ ], , -

.

] , . 10 . [ 40% , 2% ] [ 40% ] . / 6-12%. . . [ ], , , , APL , paraoxonase [ low density lipoprotein], ,. LDL/VLDL . ] , . => : ] 30% , [,,] . , . . . ,, [ > 3 gr] [ ], [ < 10000/mm3, ], C3 &C4. . ] , , , , . , [ ] 50% . ] [ ] SSc . ] [ APL- ] ] , . ] [shrinking lung syndrome] / .

] , [ ]. => , , , , , , . [20-25% ]. [ ,,], / [ ] . , . . 10% . [ ] 25% . [, ,] . . [Lupoid hepatitis] 1956 Bearn . , [ 10% ACR ]. Budd-Chiari [ ]. 10% . . ,,,, . . / . . [< 2% ] . protein-losing . => / cotton-woo [ / , . . / /cytoid bodies] . . , .

=> . [ ] . . ] : . . Fe . , / /. [ < 10% ]. [ ], [ Coombs test] . Coombs . . . ] [ < 4000cells/mm3] [ < 1500 cells/mm3] , . 5 mg/day / , 2500 WBC [70% Neu,20% Lym,8% Mono,2% Eos], , . . 30-40% - . [ ]. ] [ 50000-100000 cells/ mm3] , [ < 20000 cells/mm3] . . , . , - . .: 1] PLTs > 80000 , 2] PLTs < 80.000 > 50.000 1 mg/kg/day 4-6 10% [ < 10mg/day].A -

. , [800 mg/day, ] [2.5 mg/kg/day 100-200mg/day], 3] A PLTs < 50.000 > 20.000 [2] , 4] PLTs < 20.000 IV-IgG [ 400mg/kg/day 5 1 gr/kg/day 2 ]. . IV-IgG Fc- T-. , IV-IgG . [1] [2]. , [ ] []. ] [] 5 , , , . . , [ Coombs] , . , . IgG von Willebrand. von Willebrand [ ] , . : [ von Willebrand], [ ]. ,, , + . + [ ] : SLE [ , , ] . : ] . 15 [UK] 30 [USA]. [ ,

,], , ,, ] : [ 130/80 mmHg], [ LDL < 130], , [ 1-5 mg/day, 25 mg/day,B12 500 mg/day, ], [80 mg/ day], ] [ ], ] , , [ -],, ] [ ] . . . [ ] . [Recombinant] -, ] /warfarin [ , , / , Cox-2 , , ], ] OCP [] : placebo SELENA [0.625+5 mg / placebo 12 / 216 ], 16 228 / . : , ,Ca- & , . OCPs : , [ ], , [?], [ 31 ]. , . , , , . . , , . SERMs . , . , patch . . SELENA.

SLE, 4 NSAIDs,,, . , SLE D NSAI + + + + + + + + + + + + + + + + + + + + + + ?a + + + ? ? + + + + + ? + + + ? ?

a

. Note: + = , = , ? = / .

Malar/discoid rash .Raynaud's

: 1. . . , . IV , , 2. animal models, , 3. 10 mg Fish Oil per os, , 4. - [IVIG] , gravis. , . , IVIG , IV , 5. , . , 6. . teroid sparer -

, 7. [-/DHEA, /Danazol] , 8. T , [ ] . , 9. rituximab [Mabthera], CD-20 -, , 10. [stem cells] [ ], . /CD34 [ , G-CSF ], [ ] / T-cells. 10-15 . , [ ], 11. [1 mg/ kg/day 60 80 mg/day] , , [PLT < 30.000/mm3], , , , [// ], . . : . 1. LJP-394 - anti dsDNA . 4 Ig anti-dsDNA, -. animal models LJP-394 ds-DNA . [ I,10 50 mg ] anti-dsDNA , placebo. LJP-394 , , 2. IL-10 6 21 . , 6 . anti IL-10 [ ] . anti TNF , anti dsDNA lupus-like .

CD-40 Ligand [CD40 CD40L interaction] CTLA-4 [CD28 B7 interaction] . CD-40 Ligand, . SLE : 1. Sjogrens 20% . anti-Ro anti-La, 2. 5-10% , , 3. [ ] 5% , 4. 1% gravis, 5. . , . 1 2% , overlap [ RUPUS] => [a-PL] , . / , , [ a-PL ], [ , , ], . APS . [ ]. aPL , [ 2GP1] . - , 34% 44% . [3% ] , [ ]. Lupus nephritis. [APS] . aPL , , , .

[ SLE] APS , . => [10 ]. 2 , 50% [ 35% ]. , 12% . , . : ] CR-1 . CR-1 C3b . , , ] MBL [Mannose-binding Lectin], C- Ca C1q. MBL C2,C3, C4 . 3 [ ], ] , , ] [ 300mg] [ ]. : [eisseria ] [ ],, Histoplasma capsulatum [ ], [-, , - 19]. CRP : . , . CRP , [ CRP > 60 mg/l , ]. CRP, . WBC : , [ ]. WBC -

. . CRP [ , ]. : . - . , [ > 31 ] . , , . , . T-supressor cells . CD5 B- . . , , T . . . [ , , , MCTD, ], [ , , .Bechet]. , . 6 12 . , . [ ] . , . 14% 25%. - : C3/C4, anti-ds DNA , , , , , . [ ,, , , / ] , . -

[-] , , . : , , C3/C4/ CH50, anti-dsDNA. : , , , .O , / . [ . - ], [ , 7-10 , [ ] [ - ]. , , . : . . . [ 50% ]. Klinefelters [ ] . : [ 50-55 ] , , , . . . anti dsDNA . . anti-Ro anti-La , overlap Sjogrens, .

: . 4 : SLAM [Systemic Lupus Activity Measures],SLEDAI [Systemic Lupus Erythematosus Disease Activity Index],ECLAM [European Community Lupus Activity Measure], BILAG [British Isles Lupus Assessment Group]. , , , , , [ ], . , . SLICC [Systemic Lupus International Collaborating Clinics] Damage Index. [ 6 ] 12 [,, ,, , , ,, , , , ]. [Health Status Assessment] SF-20 SF-36.

=> 90% [ 30 50%]. 10 80-90% . : 5 [ , ], . , [ , ]. ] 30% 10 ] : , , , ] 10 [50 35-45 ]. , , , , , , , . ] . [ + ].

[Neonatal Lupus]T [ 60,52, 48 kDa ],anti-Ro/SSA anti-La/SSB, o [ /30% , .Sjogrens/50% ] . , IgG 20 24 . [ anti-Ro52 anti-La48] . . , - 2% anti-Ro/SSA . 33% , 25% , 20% Sjogrens, 1% , 18% . : . Ro/SSA La/SSB , . . IgG , . Ro & La . 5- [5--4] . , anti-Ro/SSA . [ ,, ] [ , HLA, ] . - . - La/SSB, . - , . - [anti-La/SSB] La/ SSB, . [ ].

. 6-7 - . : 50% . . 6 . . : 15% . [ ], [] [ ] . : 10% . , . : /. , , ,. anti-Ro/SSA QT- . : . . /. , 2% anti-Ro/SSA . Sjogrens [ ]. , 22 . , . 3 14% , 3 80%. 65% , 10% . , 2-3 . 1 [ PR > 20 sec], 2 Mobitz I [ QRS PR , QRS ] Mobitz II [PR , 2:1, 3:1, 4:1. QRS . . ], 3 [ , . ].

: ] [ ] : , / , , [], , ] : anti-Ro/SSA [ anti-Ro52] [ Sjogrens ]. : anti-Ro/SSA & La/SSB 16 32 [ ]. . IVIG [ -] , anti-Ro & anti-La , . : [ 11- ]. , , . 3 [ > 2 ] : echo . . 3 [ < 2 ] : 4 mg/day Per Os 6 . [ 3 2 1 ] . 1 [ PR], 2 , 2 3 , 4 mg/day Per Os . , ,/ , 4 mg/day Per Os . anti TGF [3 ] . [*] anti-Ro/SSA => anti-Ro/SSA ,. Sjogrens , . Ro/SSA . 0% 75% . ,

. . O [Drug induced Lupus]