Nghin cu p dng cc tiu chun chn on bnh Still ngi ln|Y a khoa

Nghin cu p dng cc tiu chun chn on bnh Still ngi ln

t vn Bnh Still ngi ln (Adult onset Stills disease) l mt bnh vim c tnh cht h thng, cha r nguyn nhn. y l mt trong nhng bnh khp him gp. Bnh thng xut hin tui tr, la tui hay gp nht l 16-35 tui [7].Triu chng lm sng c trng ca bnh l st cao c nh, c ban ngoi da, au khp v nh hng n nhiu c quan ni tng. George Friderick Still , bc s nhi khoa ngi Anh l ngi u tin m t bnh ny vo nm 1897 vi 22 trng hp vim khp mn tnh tr em vi cc biu hin vim khp v st khng r nguyn nhn. Nm 1971, Eric Bywater m t 14 trng hp u tin c cc triu chng bnh tng t song xy ra ngi ln [57,12]. T n nay, nhiu tc gi cng nhn bnh Still ngi ln v bnh c m s M06.1 theo ICD 10. Bnh Still ngi ln l mt bnh him gp. Theo c tnh Nht Bn c khong 10 trng hp bnh trn 1 triu dn (Cc nghin cu dao ng trong khong t 7,3 n 14,7 ngi mc bnh trn 1 triu dn). S ngi bnh mi pht hin trong 1 nm l 2 n 3 ngi bnh trn 1 triu dn [39]. Php c tnh c khong 1 n 2 ngi bnh mi c chn on trn 1 triu dn trong 1 nm [40]. Vit nam cha c s liu v t l mc bnh trong cng ng. Cc triu chng lm sng v xt nghim ca bnh Still ngi ln khng c hiu. Cc triu chng lm sng ni bt l st cao, au khp hoc vim khp, ban ngoi da. Cc triu chng xt nghim lin quan n qu trnhvim v s c mt ca cc cytokine nh: mu lng tng, protein phn ng C tng, bch cu tng, feritin huyt thanh tngCc xt nghim v min dch nh yu t dng thp, khng th khng nhn u m tnh. Khng bao gi c bng chng ca nhim khun. Do cc triu chng lm sng v cn lm sng tn mt nh trn nn chn on bnh Still ngi ln thng kh chn on, c bit giai on u. Trn th gii c rt nhiu nghin cu v bnh Still ngi ln t nguyn nhn gy bnh, c ch bnh sinh, c im lm sng cho n cc tiu chun chn on v iu tr. V c rt nhiu tc gi cc nc khc nhau ngh cc tiu chun khc nhau vi nhy, c hiu khc nhau, trong s tiu chun ca Yamaguchi c s dng rng ri hn c. Vit nam bnh Still ngi ln cn t c quan tm, hu nh ch c mt vi nghin cu v bnh ny. Trn thc t lm sng, a s cc trng hp mc bnh nhn mc bnh Still ngi ln c chn on xc nh mun, sau khi loi tr cc bnh khc nh: bnh ung th, bnh mu c tnh, bnh lupus ban h thng, bnh vim khp phn ng, bnh nhim khunV vy, chng ti tin hnh ti: Nghin cu p dng cc tiu chun chn on bnh Still ngi ln nhm 2 mc tiu: 1. M t cc c im lm sng, cn lm sng ca bnh Still ngi ln theo tiu chun ca Yamaguchi. 2. Gp phn xy dng tiu chun chn on bnh Still ngi ln ti Vit nam.Chng 1Tng quan1.1. i cng v Bnh Still ngi ln

1.1.1. Khi nim

Bnh Still ngi ln l mt bnh vim h thng cha r nguyn nhn, l mt bnh khp him gp. Bnh c mang tn gio s, bc s nhi khoa ni ting ngi Anh George Friderick Still, ngi u tin m t bnh ny tr em vo nm 1987. Triu chng lm sng ni bt ca bnh l st, au khp, vim khp, ban mu hng c hi, vim hng, lot hng, au c [8,41]. Cc xt nghim v min dch lun lun m tnh, khng bao gi c bng chng ca nhim khun. Tuy nhin, bilan vim dng tnh r rt vi TML, CRP, BC tng cao [10, 43].1.1.2. Dch t hc

Bnh Still ngi ln c bit n trong tt c cc nc v mi dn tc [11]. Hng trm trng hp c cng b di dng nhm bnh hoc cc trng hp bnh ring l theo tng biu hin lm sng [9]. Hin nay, theo bng phn loi quc t bnh tt, bnh Still ngi ln c m s M06.1.T l mc bnh dao ng ty theo thng k ca mi quc gia. Ti Nht bn, t l hin mc khong 10 trng hp bnh trn 1 triu dn (cc nghin cu dao ng trong khong 7,3 14,7 trng hp bnh trn 1 triu dn). S ngi bnh mi pht hin trong 1 nm Nht bn l khong 2 3 ngi bnh /1 triu dn [39].Theo thng k ti vng Brittany v Loire ca Php t l hin mc khong 1-2 ngi bnh / 1 triu dn [40].Quan im v bnh Still ngi ln hin cn ang c tranh ci. Mt s tc gi ch chp nhn nhng trng hp khi pht ln u ngi ln. Mt s khc chp nhn c nhng bnh nhn c tin s bnh Still tr em v n tui trng thnh ti pht li. Khong thi gian ti pht ny l khng c nh, i khi c th l hng chc nm. Qu trnh din bin ny c m t qua 34 trng hp c tin s bnh Still tr em trn tng s 180 trng hp bnh Still ngi ln do Ohta thu thp [37].Theo M.F. Kahn, M Delaire [55] cc trng hp bnh pht trin lin mch t lc b khng c xem l bnh Still ngi ln .Bnh Still ngi ln thng xut hin ngi tr, la tui hay gp nht l 16-35 tui. C 4 trng hp th c 3 trng hp bnh bt u xut hin tui 16-35 [13,21]. Tuy nhin, trong nhng trng hp him gp, bnh ny c th khi pht kh mun: c mt trng hp bnh Still ngi ln do Steff v Cooke m t mt bnh nhn 70 tui [44].Ni chung, bnh Still ngi ln l mt trong nhng bnh khp him gp, t c quan tm chn on. Vit nam, hin nay cha c s liu v t l hin mc trong cng ng.1.1.3. Sinh l bnh

Bnh nguyn ca bnh Still ngi ln hin nay cha r. Mt s gi thuyt cho rng y l bnh c yu t di truyn. Mt s tc gi khc li cho rng bnh Still ngi ln l mt tnh trng phn ng ca c th sau nhim cc virusYu t di truyn hc Nghin cu v di truyn hc cho thy bnh Still ngi ln c lin quan ti h thng HLA-B17, B18, B15 v DR2. Tuy nhin, trong mt nghin cu khc n li lin quan ti cc yu t HLA-B14 v DR7 hoc BW35 v CW4 hoc DR4 v DW6 [20].Yu t nhim khunC gi thuyt cho rng bnh Still ngi ln l mt tnh trng phn ng ca c th sau nhim cc virus: adenovirus, enterovirus 7, cytomegalovirus, Epstein-barrvirus, parainfluenza, coxsackie B4, influenza A, parvovirus B19 [4,22]Mt s nghin cu khc li cho rng nguyn nhn t cc vi khun bao gm: Mycoplasma pneumonia, chlamydia pneumonia, Yersinia enterocolitica 3 v 9, Brubella abortus v Borrelia burgdoferi [52]Cc nghin cu gn y cho thy cc sn phm cytokine gi vai tr quan trng trong bnh sinh ca bnh Still ngi ln nh IL-2, IL-6, TNF anpha, IFN, IL-18 [16,26,27].1.1.4. Triu chng lm sng

- St: st l triu chng gp hu ht cc bnh nhn. Bnh nhn thng st cao trn 39oC, st cao thnh cn, rt run, t nht l 4 gi. St cao hng ngy hoc st cch nht v thng st vo chiu ti v sng sm [22,43]. St cao c th km theo cc triu chng: vim thanh mc, au hng, au c, au khp . a s bnh nhn xut hin st sau mi xut hin au khp.au khp, au c thng tng ln trong cn st. Mt s bnh nhn xut hin au hng trc khi xut hin st.St ko di nhiu tun lin, bnh nhn gy st, suy kit trn lm sng nhiu khi bc s chn on nhm vi mt bnh nhim khun hoc mt bnh h thng. C ch gy st y l do cc cytokin nh IL-1, IL-6, TNF alpha thng qua prostaglandin E2 tc ng ln th th trung tm iu nhit gy ra. Nhp tim thng nhanh trong lc st cao c th n 120 ln/pht. Tuy nhin, ht st nhp tim li tr v bnh thng.- au khp v/hoc vim khp: triu chng ny gp vi t l 64-100% bnh nhn. Cc khp hay b tn thng l khp gi, khp bn c tay, bn c chn, khp khuu tay, khp vai. C th vim mt khp hoc vim a khp.Vim khp c tnh cht i xng [6,7]. Triu chng vim khp, au khp thng xut hin km theo triu chng st v gim dn khi ht st. y l c im cn phn bit vi bnh vim khp dng thp. Trong a s trng hp, cc khp vim khng b bin dng, b dnh khp hay b lch trc nh bnh vim khp dng thp [51]. Cc khp vim din bin tng t km theo vi st cao v c th c trn dch khp gi. Xt nghim dch khp ch yu l BC, chim u th l BCNTT. Cc du hiu cng khp thng xut hin sau khi bnh nhn b bnh 2-3 nm ( th vim khp mn tnh).- Ban ngoi da: c im ca ban l xut hin bt k v tr no, khng c nh. Thng gp hn c gc chi v lng him khi ban xut hin mt, u chi. Ban in hnh c mu hi c hi [23,25]. Ban c hnh dng ging nh ban trong bnh si, hnh thnh t cc vt trn da, t vi milimt n vi centimt. Tm vt sng hn mt cht [12]Ban xut hin c th km cm gic nga nn nhiu khi nhm vi ban d ng thuc.Cc ban thng xut hin trong khi st cao v bin mt khi h st. V mt m bnh hc ca ban trong bnh Still ngi ln, theo nghin cu ca Elkon v Coll [11], Noyon v Coll[55], trong 4 trng hp quan st nhn thy lp biu b di da b ph n ng thi c hin tng thm nhim t bo n nhn v tng sinh mch xung quanh. Triu chng m bnh hc ny khng c hiu song c th cho php phn bit bnh Still ngi ln vi cc hi chng c tn thng v da v khp. V d nh trong hi chng Sweet hoc bnh ngoi da c st v tng bch cu trung tnh cp tnh .

Hnh 1.1. Ban mu hng c hi (trch dn t: Website Khoa Y i Hc Lille 2 http://medecine.univ-lille2.fr/pedagogie/contenu/discipl/med-interne/still-cours.pdf).

Hnh 1.2. Ban dng bnh si (trch dn t: Website Khoa Y i Hc Lille 2 http://medecine.univ-lille2.fr/pedagogie/contenu/discipl/med-interne/still-cours.pdf).Theo nhiu tc gi m t th b ba triu chng st, vim khp hoc au khp, ban ngoi da thng i km vi nhau trn lm sng v l nhng du hiu gi chn on bnh Still ngi ln [55,56].- au c: au c l triu chng thng gp vi t l 56-84% bnh nhn v xut hin i km vi st [44,30,27,23]. Vim a c rt him gp, mt s trng hp bnh nhn c tng enzym c (CK) trong huyt thanh nhng mc nh [25]. Cc thm d v in c v sinh thit c cho kt qu bnh thng [9].- Vim hng: C khong 50% bnh nhn c triu chng vim hng, lot hng. Ban u triu chng ny gy lc hng chn on a s cc trng hp: nhiu bnh nhn c chn on l thp khp cp hoc mt bnh nhim khun [28]Nguyn nhn ca vim hng dung nh xut pht t s qu sn ca cc hch bch huyt [36].- Gan, lch, hch: Hch to cng rt thng gp v i khi c th b chn on nhm vi mt bnh l hch ngoi bin. Gan to, lch to gp khong 50-70% bnh nhn. C th pht hin gan lch to trn lm sng hoc i khi ch c th pht hin qua siu m.Tn thng hy hoi t bo gan t nhiu lin quan n iu tr thuc chng vim gim au [13]. Tuy nhin, trn thc t y thng l nhng tn thng nguyn pht ca bnh Still ngi ln [52]. Sinh thit gan thy du hiu vim nh khong ca v thm nhim t bo n nhn.Mt s bnh nhn c biu au qun vng bng di. Triu chng ny c th gii thch bi s xut hin hch trong bng hoc trn dch mng bng [28].-Triu chng tim mch: Trn dch mng tim, vim mng ngoi tim gp 23,8% bnh nhn [42]. Cc bin chng tim mch c th c nhng him gp nh nhi mu c tim, vim c tim [35].- Tn thng phi: Tn thng phi bao gm trn dch mng phi, x ha phi; ph phi cp tn thng him gp hn[45].- Cc triu chng khc + Bnh l thn rt him gp nh: vim cu thn, nhim bt thn [50].+ C th c cc bin chng ca bnh mu nh: huyt khi, xut huyt gim tiu cu, hi chng Miller- Fischer [30,28,41,7].+ Tn thng h thn kinh rt him gp. Mt s hn hu cc trng hp c gp tn thng trung ng (hi chng thp, co git) v cc vng ngoi bin c bit l tn thng dy thn kinh s no.+ Mt rt t khi b tn thng v nu c th hu nh ch l s trng hp ngu nhin.1.1.5. Triu chng cn lm sng

Cc xt nghim trong bnh Still ngi ln u lin quan n h thng vim v h thng cytokine. Cc xt nghim v min dch lun m tnh v khng c bng chng ca nhim khun.- T bo mu ngoi vi+ S lng BC tng 15 G/L- 20 G/L hoc hn v tng ch yu l BCNTT. Tng BC l hu qu th pht ca tng sinh ty dng BC ht [24].+ S lng hng cu v tiu cu gim trong t tin trin ca bnh [32].- Huyt ty : Mt iu quan trng trong bnh Still ngi ln l mc d c s lng BC mu ngoi vi rt cao, c biu hin thiu mu nhng xt nghim huyt ty hon ton bnh thng, khng c du hiu tng sinh ty. y l mt xt nghim quan trng cn phi lm chn on phn bit bnh Still ngi ln vi cc bnh l mu cc tnh khc. - Cc xt nghim thuc bilan vim sinh hc: Cc xt nghim thuc bilan vim sinh hc biu hin tnh trng vim.+ Tc mu lng v CRP tng cao 100% bnh nhn [12]. TML gi u thng tng cao hn 100 mm.+ Tng fibrin trong mu, tng alpha 2, tng gama globulin. nh lng cc globulin min dch trong mu c th thy s gia tng ca IgG v i khi c IgA v IgM.- Cc xt nghim v gan: C khong 1/3 bnh nhn bnh Still ngi ln giai on tin trin c tng LDH, AST, ALT, GGT v Bilirubin [47].Sinh thit gan c du hiu vim nh h thng ca v thm nhim t bo n nhn.- Ferritin v Glycosylated Ferritin: Ferritin l mt protein tan trong nc l kho d tr st trong c th ng sau hemoglobin (25%). Mt phn t Ferritin cha 4000-5000 ion Fe3+. Ferritin mu c nh lng bng phn ng Elisa v gi tr bnh thng l 80-200 ng/ml. Hin nay xt nghim Ferritin c s dng nhiu trong chn on bnh Still ngi ln. Ferritin l mt marker trong pha vim cp tnh v thng tng ngay t khi phn ng vim khi pht. Ferritin tng trong phn ng vim l do tng trong sn phm ph hy ca h thng i thc bo v tn thng t bo gan, mt khc, s c mt ca mt s interleukin cng lm tng Ferritin nh IL-1b, Il-18, TNF alpha, IL-6 [38,49].Hin nay trn th gii nh lng c mt dng ng phn ca Ferritin l Glycosylated Ferritin. Theo nghin cu ca Fautre v cng s [14,17], gi tr chn on ca Ferritin v Glycosylated Ferritin trong bnh Still ngi ln nh sau* Ferritin mu trn 5 ln gii hn bnh thng: c nhy 38,9%, c hiu 81,5%, OR: 2,81.* Glycosylated Ferritin di 20%: c nhy 70,5%, c hiu 83,2%, OR: 8,16.* Ferritin mu > 5 ln gii hn bnh thng v Glycosylated Ferritin < 20%: c nhy 43,2%, c hiu 92,9%, OR: 8,11.Hn na, theo mt s tc gi, Ferritin cn c coi nh mt marker nh gi mc hat ng ca bnh v Ferritin tng ln trong giai on cp v gim i khi lui bnh [20,21]. C mi tng quan cht ch gia TML, CRP v Ferritin trong giai on cp.- Cc xt nghim m tnh quan trng trong bnh Still ngi ln: KTKN, RF m tnh; cy mu m tnh; ty bnh thng.- X quang xng khpTrong bnh Still ngi ln, khng c s thay i r rng v xng khp trn phim X quang trong giai on sm ca bnh. Tuy nhin c th thy mt s hnh nh khng c hiu nh ph n phn mm, trn dch khp ...Tn thng hp khe khp bn c tay trn phim X quang c th xut hin sau 6 thng b bnh.- Protein S100A12: protein gn canxi S100A12, l mt du n chn on bnh Still ngi ln [3].Thng 6 - 2003, cc nh nghin cu ngi c tm ra mt du n r rt cho php ci thin kh nng chn on sm v chnh xc bnh Still ngi ln., l protein S100A12. Cc tc gi xem xt nng protein gn canxi S100A12 33 bnh nhn b bnh Still, 15 ngi b nhim khun hoc b nhim trng mu nng v 37 ngi i chng khe mnh. S100A12 biu hin BCTT, khi phn ng vi th th a phi th cho sn phm gluco ha cui cng c tc dng tr vim. Cc a hnh thi ca th th ny c vai tr trong vim khp mn. Nng S100A12 huyt thanh trung bnh nhm i chng khe mnh l 50 ng/ml, trong khi nhng ngi c bnh ang hat ng cao hn nhiu (2650 ng/ml). Tuy nhin nhng bnh nhn b bnh Still ang thuyn gim c nng thp hn nhiu (75 ng/ml). Bnh nhn b nhim trng nng c nng mc trung gian (630 ng/ml).Li ch c bn ca du n ny l cung cp mt cng c cho php chn on bnh Still nhanh hn v chnh xc hn, cho php theo di iu tr thch hp hn.1.1.6. Chn on bnh Still ngi ln

- Tiu chun chn onHin nay c rt nhiu tiu chun chn on bnh Still ngi ln, mi tiu chun c mt nhy khc nhau nh tiu chun Yamaguchi, Cush, Fautre. Cc tiu chun ny thng da trn cc triu chng chnh nh st ko di trn mt tun; au khp; ban in hnh mu hng c hi thng xut hin trong lc st; s lng BC > 10.000/ mm3 trong 80% l BCNTT; vim lot hng; hch v/hoc lch to mi pht trin; mt s enzym tng. Ngoi ra cc triu chng m tnh cng rt quan trng: RF v v khng th khng nhn m tnh; khng c nhim khun, loi tr cc bnh c tnh, c bit u lympho hoc bnh thp khp, c bit vim nt quanh ng mch v vim mch dng thp...Bng tm tt cc tiu chun chn on bnh Still ngi ln Tn TCNi dungYamaguchi [53]Cush [24]Fautre [15]

Tiu chun chnh1.St t 39o C tr ln t nht mt tun.2.au khp t 2 tun tr ln.3.Ban in hnh mu hng c hi thng xut hin trong lc st.4.BC > 10 G/L trong 80% l BCNTT1.St t 39oC tr ln.2.Ban mu c hi3.BC tng >12 G/L + TML >40 mm/h4.KTKN m tnh, RF m tnh5.Cng khp c tay* mi tiu chun c tnh 2 im1. St cao c nh > 39oC2. au khp3. Ban mu hng c hi4. Vim hng5. BCNTT 80%6.Glycosylated Ferritin 20%

Tiu chun ph1.Vim lot hng2. Hch v/hoc lch to mi phttrin. Hch sng au r,lch to xc nh khi s hoc siu m3.Chc nng gan ri lon:tng transaminase v/hoc LDH, khng do nhim c thuc hoc d ng4.RF v KTKN m tnh1.Khi bnh nh hn 35 tui2.Vim khp3.au hng hoc vim lot hng4.Vim a mng.5.Cng c chn hoc ct sng c*Mi tiu chun c tnh 1 im1.Ban khng c nh2.Bch cu tng > 10 G/L

Tiu chun loi tr1.Nhim trng, c bit nhim khun v nhim khun tng BCNTT2.Bnh c tnh, c bit u lympho3.Bnh thp khp, c bit vim nt quanh ng mch v vim mch dng thp

Chn on xc nhC 5 tiu chun, trong c t nht 2 tiu chun chnh v khng c tiu chun loi tr-Chn on nghi ng: t 10 im vi 12 tun theo di.-Chn on xc nh: t 10 im vi 6 thng theo di.-C 4 tiu chun chnh-Hoc 3 tiu chun chnh + 2 tiu chun ph

Tn TCNi dungReginatoCalabroKahn

StChnhDai dng, tng cnChnh>39oCChnhCao c nh > 2 tun

Bch cu muChnhPh> 15 G/LChnh> 12 G/L

Ban mu hng c hiChnhChnhChnh

Vim khp hoc au khpChnhVim nhiu khp hoc mt khpChnhVim khp hoc au khpChnh: vim khpPh:au khp

au cChnhPh

b bnh trong thi k thiu ninChnh

au hngPhPh

Vim a mngPhPhVim mng phi, vim mng ngoi tim,vim c timPhVim mng ngoi tim

Hch toPhPh

Lch toPhPh

Gan toPh

Tng enzym ganPhPh

RF v KTKN m tnhLoi trChnhLoi tr

Chn on xc nh4 tiu chun chnh4 chnh + 2 ph4 chnh hoc 3 chnh + 3 ph

- nhy ca cc tiu chun chn on theo hai nghin cu khc nhau ca Masson (1996) [32] v Yamaguchi (1992) [53] Kt qu NCTiu chun CKt lun ca nghin cu Masson (1996)Kt lun ca nghin cu Yamaguchi (1992)

Yamaguchi93,5 %96,2 %

Cush80,6 %80,0 %

Calabro80,6 %60,9 %

Reginato55,2 %51,2 %

Kahn69,3 %

- Chn on phn bitbnh Still ngi ln Cc triu chng ca bnh Still ngi ln l khng c hiu nn trc khi a ra chn on xc nh bnh ny cn phi chn on phn bit vi cc bnh nh cc bnh nhim khun, bnh ung th, bnh t min dch+ Cc hi chng nhim virus nh rubella, epstein-virus, virus thy u, adenovirus cng cn phi chn on loi tr nu cc triu chng ny tn ti trn 3 thng+ Cc bnh c tnh: bnh bch cu cp, lymphoma, u nguyn bo bch huyt+ Mt s tnh trng bnh khc cng c th chn on nhm vi bnh Still ngi ln nh bnh vim khp phn ng, cc bnh thuc nhm bnh l ct sng huyt thanh m tnh khc, hi chng Kikuchis, hi chng Sweets, vim mao mch...1.1.7. Tin trin v tin lng

C ba th lm sng ca bnh Still ngi ln c phn loi theo cc triu chng lm sng, tin trin v tin lng bnh.- Th nh (th t hn ch bnh)Th nh l th c cc triu chng bnh h thng nh: st, ban da, vim thanh mc, gan, lch, hch to. Hu ht cc bnh nhn trong th ny u khi bnh trong vng 1 nm k t khi bnh khi pht.- Th trung bnh (th bn cp) Trong th trung bnh, bnh nhn c nhiu t tin trin ca bnh, c hoc khng c cc triu chng v khp. Cc t n nh bnh ko di vi thng hoc vi nm. Cc t tin trin bnh sau ny thng nh hn khi bnh khi pht.- Th vim khp mn tnhCc triu chng trong th vim khp mn tnh ch yu biu hin khp. Vim khp mn tnh c th dn n tn thng ti khp. C khong 67% bnh nhn trong nhm ny c tn thng khp nng n v c ch nh thay khp sau 3-5 nm b bnh. Bnh nhn bnh Still ngi ln c biu hin vim khp mn tnh c tin trin v tin lng bnh nng hn bnh nhn ch tn thng h thng c quan n thun. Cc th c tn thng ban da, vim a khp c bit l cc khp gc chi thng tin trin thnh th vim khp mn tnh. Bnh nhn c tn thng h thng c quan thng c tin lng tt hn rt t c cc bin chng vim mng ngoi tim, bnh nhim bt, bnh gan, suy h hp 1.1.8. iu tr bnh Still ngi ln

1.1.8.1. Mc ch iu tr

- iu tr triu chng: h st, chng vim khp, gim au khp...- c ch phn ng min dch qu mc ca c th.- Trnh cc bin chng ca bnh v ca cc thuc iu tr.- Gio dc, t vn cho bnh nhn.1.1.8.2. iu tr c th

- Thuc chng vim khng steroidCh nh: giai on vim khp, au khp. iu tr thuc chng vim khng steroid n thun ch c hiu qu 15% bnh nhn. Lu cc chng ch nh ca thuc.Cc nhm thuc: diclofenac, piroxicam, meloxicam, celecoxib... Liu thuc c ch nh da trn nguyn tc liu ti thiu c hiu qu.GlucocorticoidCh nh: Theo nghin cu ca Wouters [50], glucocorticoid c th kim sot c triu chng khp v cc tn thng c quan trn 76% bnh nhn. Liu corticoid Trng hp bnh nng thng dng minibolus, truyn tnh mch 80-125 mg methylprednisolon pha trong 250 ml dung dch sinh l trong 3-5 ngy lin tip. Sau liu ny duy tr tip tc bng ng ung liu 1,5- 2 mg/kg/24h tnh theo prednisolon.Trng hp bnh mc trung bnh: 1- 1,5 mg/kg/24h, gim dn 10% liu ang dng mi tun ty theo triu chng lm sng v xt nghim.Duy tr liu 10-15 mg/ngy trong 6 thng kim sot bnh v trnh cc tn thng trm trng ti khp. Cc thuc iu tr c bnTrong trng hp bnh nhn bnh Still ngi ln khng p ng tt vi corticoid phi kt hp vi cc thuc khc nh: cyclosporin A, Hydroxychloroquin, mui vng, D-penicillamin, azathioprin, cyclophosphamid Methotrexat kim sot c hiu qu 40% s trng hp .Cc phng php khc+ Truyn gamaglobulin c hiu qu i vi cc trng hp bnh khng p ng vi cc thuc vi liu 0,4-2 gam/kg/ngy trong 2-5 ngy. Liu php iu tr ny c th kim sot thi gian lui bnh ca bnh nhn t 2-53 thng.+ Hin nay theo kt qu nghin cu ca Cavagna v Caporali cho thy iu tr nhm thuc c ch TNF (Etanercept, Infliximab) kt hp vi methotrexat trong iu tr bnh Still ngi ln c kt qu rt tt, ci thin cc triu chng lm sng v kim sot c bnh trong vng 2 tun sau khi iu tr. [7]+ Liu php iu tr mi nht hin nay l dng cc ch phm c ch Interleukin (IL-6, IL-1: Anakinra 100 mg/ngy tim di da) iu tr bnh cc bnh nhn bnh Still ngi ln khng p ng vi cc thuc corticoid v cc thuc c ch min dch. Vi liu php ny bnh nhn bnh Still ngi ln kim sot c 70% v gim c cc tc dng ph nguy him khi dng cc thuc c ch TNF [19,30].1.2. TNH HNH NGHIN CU bnh Still ngi ln TRN TH GII V TI VIT NAM1.2.1. Trn th giiNm 1897, George Fredrich Still ln u tin m t bnh Still tr em vi 22 trng hp bnh vim khp mn tnh tr em vi cc biu hin vim khp v st khng r nguyn nhn.Nm 1971, Eric Bywater m t 14 trng hp bnh ngi ln cng vi cc triu trng st, vim khp, au khp, ban ngoi da.T ti nay c rt nhiu nghin cu v bnh Still ngi ln t nguyn nhn, c ch bnh sinh, c im lm sng, tiu chun chn on v iu tr.Nm 1992, Yamaguchi v cc cng s ngi Nht Bn a ra tiu chun chn on bnh Still ngi ln c nhy 96,2% v c hiu 92,1% [53]. Tiu chun Yamaguchi bao gm 4 tiu chun chnh, 4 tiu chun ph v 3 tiu chun loi tr c xy dng da trn cc triu chng lm sng v cn lm sng in hnh. y l mt tiu chun d p dng trong thc hnh lm sng c nhy v c hiu cao c nhiu nh nghin cu s dng lm tiu chun la chn bnh nhn nghin cu.Fautrel B v cc cng s ngi Php li c rt nhiu nghin cu ni ln vai tr ca Ferritin v Glycosylated ferritin trong chn on bnh Still ngi ln [14].+ Nhng nm 2000- 2001, mt s nghin cu cho thy vai tr ca ferritin huyt thanh trong bnh Still ngi ln. T l % Glycosylated ferritin huyt thanh thp trong sut tin trnh bnh Still ngi ln [41]. Kt qu ca mt nghin cu a trung tm vi 205 bnh nhn kt lun: Ferritin v Glycosylated ferritin c gi tr rt cao trong chn on bnh Still ngi ln. Trong thc hnh lm sng c th p dng rt hu ch cho cc chn on phn bit [17].C rt nhiu tc gi vi cc cng trnh nghin cu nhm tm hiu nguyn nhn, c ch bnh sinh bnh Still ngi ln, c bit l mi lin quan vi cc virus: + AS Luder -1989, v cng s cho rng bnh Still ngi ln lin quan vi nhim adenovirus [4]. Francisco Javier Ecudero v cng s- 2000 nhn thy s nhim Rubella v bnh Still ngi ln Francisco Javier Ecudero nghi ng c phi parvovirus B19 gy nn bnh Still ngi ln [18]. Izumikawa K -2007 cho rng bnh Still ngi ln lin quan vi nhim cytomegalovirus [22]. Fujita M- 2009 tm thy cc bng chng nhim chlamydia pneumonia v bnh Still ngi ln+ Nm 2005, Fautrel B v cng s nu vai tr ca TNF anpha trong bnh sinh ca bnh Still ngi ln [16].V iu tr bnh Still ngi ln, c rt nhiu nghin cu v iu tr bnh Still ngi ln. Kt qu ca Methotrexat trong iu tr bnh Still ngi ln c chng minh qua nghin cu ca Takao Fujii v cng s - 1997 . Yamaguchi, Ohta- 1998 cng khng nh hiu qu ca methotrexat trong trng hp bnh Still ngi ln c gim TC mu ngoi vi [54].Gn y c rt nhiu nghin cu ni v vai tr ca ch phm sinh hc nh trong iu tr bnh Still ngi ln: nghin cu dng Infliximab ca Cavaggna - 2001 [7].; iu tr vi rituximab ca K Ahmadi Simab- 2006 [29]; thuc c ch IL1 (Anakinra) ca mt s tc gi nh Lequerr T v cng s - 2008 [46], Kotter - 2007 [30].1.2.2. Vit namDng nh c rt t nghin cu v bnh Still ngi ln ti Vit Nam. Nm 2007, ln u tin Trn Th Minh Hoa tin hnh mt nghin cu hi cu m t ct ngang vi tn ti Nhn xt bnh Still ngi ln iu tr ti khoa c xng khp bnh vin Bch Mai trong 2 nm t thng 05/2005 n thng 05/2007 . Nghin cu ny bc u nu c mt s c im lm sng, cn lm sng ca bnh Still ngi ln Vit Nam [2]. Ngoi ra, chng ti khng tm thy nghin cu no khc v bnh ny.Chng 2I TNG V PHNG PHP NGHIN CU2.1. i tng nghin cu

i tng nghin cu gm 37 bnh nhn c chn on bnh Still ngi ln theo tiu chun Yamaguchi (1992) iu tr ni tr ti khoa C xng khp Bnh vin Bch Mai t thng 1/2005 10/2009 (gm 30 bnh nhn hi cu t 1/2005 10/2008 v 7 bnh nhn tin cu t 10/2008 10/2009).2.1.1. Tiu chun chn i tng nghin cu

p ng cc tiu chun sau: c chn on bnh Still ngi ln theo tiu chun Yamaguchi (1992).+ i vi cc bnh nhn hi cu phi c y h s, giy t lu li cc thng tin p ng tiu chun Yamaguchi.+ i vi bnh nhn tin cu chp nhn tham gia nghin cu.2.1.2. Tiu chun loi i tng nghin cu

- i vi cc bnh nhn hi cu: Bnh nhn c bc s trong khoa chn on bnh Still ngi ln song khng lu h s, giy t c cc thng tin p ng tiu chun Yamaguchi.- i vi bnh nhn tin cu: khng chp nhn tham gia nghin cu (tin cu).2.2. phng php nghin cu

2.2.1. Thit k nghin cu

Nghin cu tin cu kt hp hi cu theo phng php m t ct ngang.- Bnh nhn tin cu c hi bnh, thm khm lm sng, lm xt nghim theo mt mu bnh n nghin cu thng nht.- Bnh nhn hi cu c tng kt cc triu chng lm sng, cn lm sng, tin s bnh t bnh n lu tr sang mt mu bnh n nghin cu thng nht.2.2.2. Phng php thu thp thng tin

Mi i tng nghin cu c mt bnh n mu bao gm phn hi bnh, thm khm v xt nghim.2.2.2.1. Hi bnh- Hnh chnh: tn, tui, gii, ngh nghip, a ch, in thoi lin lc.- Khai thc tin s:

+ Bn thn: Bnh ni khoa mc, cc thuc iu tr.

Tin s bnh vim khp mn tnh thiu nin, bnh Still tr em hoc bnh Still ngi ln cc t tin trin.+ Gia nh: C ngi thn b bnh h thng, bnh c xng khp hay cc bnh ni khoa khc.- Khai thc bnh s:+ Thi gian din bin bnh.+ Triu chng u tin xut hin+ Triu chng st:. Bnh nhn c st khng ? tnh cht st ? cc triu chng i km trong lc st: au khp, au c, ban ngoi da . . Ht st cc triu chng trn c gim khng ? . Cc thuc h st dng: tn thuc, liu, p ng ca triu chng.+ au khp, vim khp:. Thi gian au khp. V tr au khp. Tnh cht au khp: au c tnh cht i xng, au kiu vim. C sng, nng, hay khng ?. C cng khp hay khng ?

+ Ban ngoi da:

. Ban xut hin khi no ?

. Ban c xut hin trong lc cao khng ?

. Tnh cht ban : Ban mu hng c hi, ban kiu d ng.

. V tr xut hin ban

+ au c

+ au hng: c lot hng khng ?

+ au bng

+ C s thy hch mi xut hin khng ? + Khai thc tnh trng gy st (nu c): s cn mt, khong thi gian mt cn2.2.2.2. Khm lm sng- Ton thn:+ m mch, o huyt p, nhit + Th trng: theo BMI p dng cho ngi chu .+ Ph+Hch ngoi bin+Ban ngoi da - Khm b phn+ C xng khp:. C au khp hay vim khp khng ?. V tr, tnh cht au.. C trn dch khp khng ?+ Nghe tim: nhp tim, ting tim, ting thi bt thng, lu pht hin cc triu chng vim mng ngoi tim+ Phi: r ro ph nang, cc ting ran bt thng, lu pht hin triu chng trn dch mng phi + Bng: dch c chng, gan to, lch to.+ Hng: vim hng, lot hng.2.2.2.3. Xt nghim- Xt nghim t bo mu ngoi vi, TML, huyt ty c thc hin ti khoa huyt hc ti bnh vin Bch Mai.- Xt nghim v gan, thn, RF, CRP c hin ti khoa sinh ha bnh vin Bch Mai.nh gi ch s sinh haXt nghimGi tr bnh thng

Ur2,5- 7,5 (mmol/l)

CreatininNam: 62- 120 (mol/l)N : 53- 100 (mol/l)

Protein TP65- 82 (g/l)

Albumin35- 50 (g/l)

Globulin24- 38 (g/l)

GOT 37 (U/L- 37oC)

GPT 40 (U/L- 37oC)

CRP0 (mg/dl)

- Tng phn tch nc tiu: Protein niu, HC niu, BC niu.- KTKN c thc hin ti khoa D ng Min dch lm sng bnh vin Bch Mai theo phng php Elisa.+ c kt qu: dng tnh hoc m tnh.- Cy mu c thc hin ti khoa vi sinh.- Tt c cc bnh nhn tin cu u c lm siu m tim, siu m bng, chp X quang tim phi, X quang khp (chp ti v tr khp vim). + c kt qu: do cc bc s chuyn khoa tng ng c.2.2.3. S nghin cu

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