BỆNH LUPUS

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<p>I HC QUC GIA H NITrng i Hc Khoa Hc T Nhin Khoa Sinh Hc ***</p> <p>TIU LUNMIN DCH HC C S</p> <p>BNH LUPUS BAN H THNGGV Hng Dn: GS.TS.NGT Ngc Lin</p> <p>Sinh Vin : Nguyn Qunh Anh Lp : K53A Sinh Hc</p> <p>H Ni, 11/2010.1</p> <p>I HC QUC GIA H NITrng i Hc Khoa Hc T Nhin Khoa Sinh Hc ***</p> <p>TIU LUNMIN DCH HC C S</p> <p>BNH LUPUS BAN H THNGGV Hng Dn: GS.TS.NGT Ngc Lin</p> <p>Sinh Vin : Nguyn Qunh Anh Lp K53A Sinh Hc</p> <p>H Ni, 11/2010.2</p> <p>NI DUNG CHNH</p> <p>I. Gii thiu chung v min dch bnh l qu mn v bnh t min.4 II. Gii thiu chung v bnh Lupus ban h thng.7 III. Lch s nghin cu bnh Lupus ban h thng.9 IV. Lm sng11 V. Chn on cn lm sng.22 VI. C ch bnh sinh........................................................................31 VII. Tin lng............................................................................41 VIII. iu tr....43 IX. Lupus ban do thuc.45 X. Ti liu tham kho...............................................................47</p> <p>3</p> <p>I. GII THIU CHUNG V MIN DCH BNH L QU MN V CC BNH T MIN1. Min dch bnh l qu mn H min dch ca mt c th p ng li vi cng mt khng nguyn ln tip xc th hai thng mnh hn rt nhiu so vi tip xc ln u. p ng ny mang tnh c hiu nhng c th din ra qu mc v a n s tn thng nghim trng m t bo. S p ng min dch qu mc thng c gi l hin tng qu mn Hypersensitibility. Cooms v Gell phn bit 4 kiu qu mn, Roitt v cc cng s a thm mt khi nim qu mn th 5. l: Type I : qu mn phn v Anaphylactic hypersensibility Type II: qu mn gy c t bo Cytotoxic hypersensitibility Type III: qu mn do cc phc h min dch Immunocomplex hypersensibility Type IV: qu mn qua trung gian t bo, hay qu mn mun Delayed type hypersensibility Type V : qu mn do kch thch Stimulating hypersensibility</p> <p>4</p> <p>2. Bnh t min Bnh t min xy ra khi c th khi pht p ng min dch i vi mt trong nhng cu trc c th. Tn thng t chc xy ra do p ng min dch tu thuc vo v tr ca t khng nguyn. Nu t khng nguyn ny gii hn t chc hay c quan, th biu hin lm sng cng gii hn t chc v gi l bnh t min c quan. Nu t khng nguyn phn b rng ri trong c th , th tn thng cng phn tn nhng t chc khc nhau v gi l bnh t min khng c hiu c quan. Bnh vim tuyn gip l bnh tiu biu cho bnh t min c hiu c quan. p ng t min chng li t khng nguyn tuyn gip v dn n ph hu chn lc tuyn gip. Ngc li, bnh lupus ban h thng l bnh t min khng c hiu c quan. Trong trng hp ny, p ng min dch chng li cu trc nhn v dn n tn thng lan to, a dng, khng gii hn t chc hay c quan c bit; c trng cho bnh vim t chc lin kt. Th gii ang phi i mt vi t l mc cc bnh t min ngy cng tng. y l mt trong nhng nhm bnh l gy t vong hng u, lm gim tui th trung bnh 15 nm, vi chi ph iu tr hng nm c tnh trn 120 t -la M. Mi nm, c gn 10 triu ph n c chn on mc mi mt trong 7 bnh t min hay gp l lupus ban h thng, x cng b h thng, vim khp dng thp, x cng ri rc, bnh Sjogrens, bnh vim ng rut v tiu ng type 1. Theo nghin cu ti M, trong bn thp k gn y, t l mc cc bnh lupus ban h thng (SLE), x cng b h thng v vim a c tng gp 3 ln. Ti Trung tm D ng Min dch lm sng, Bnh vin Bch Mai, thng k trong 10 nm gn y cho thy, t l bnh nhn lupus ban h thng v cc bnh t min n khm v</p> <p>5</p> <p>iu tr c xu hng ngy cng tng, chim gn 60% tng s bnh nhn iu tr ni tr.</p> <p>6</p> <p>II. GII THIU CHUNG V BNH LUPUS BAN H THNGLupus ban h thng (systemic lupus erythematosus: SLE) Tn thng h thng ca cc c quan trong SLE gy nn bi s lng ng ca phc hp min dch: khng nguyn - khng th ti cc mch mu, t chc lin kt. Biu hin lm sng a dng, c trng bi cc t vng bnh v lui bnh. Cn nguyn cha r rng. T l lu hnh t 15-50 ca trn 100.000 dn. Tn thng ca bnh c c ch chung ca min dch bnh l, trong vai tr ca phc hp min dch (qu mn type III). Phc hp ny c bit l i tnh vi thn nhng vn c th lng ng nhng ni khc nh khp, da, mu, tiu ho, gan, thn kinh, h hp. S hot ho b th v s phng thch cc enzym v hot cht trung gian ca bch cu trung tnh l tc nhn gy tn thng ch yu.</p> <p>7</p> <p>8</p> <p>III. LCH S NGHIN CU BNH LUPUS BAN H THNG</p> <p>Khng ai bit chnh xc ti sao bnh li c t tn l Lupus. Y vn ghi li rng lupus l h ca mt gia nh La m c i, v vo th k th 4 sau cng nguyn c mt v gim mc x Gaul mc mt cn bnh c gi l Lupus. T lupus trong ting la tinh c c ngha l ch si. N lin tng ti tn thng ca bnh ging nh vt thng do si cn. Nm 1851 Cazanave ln u tin m t chi tit triu chng ngoi da ca mt bnh nhn : ban , dy sng, teo da v a ra thut ng: Lupus (lupus erythemateaux: LE). ng v tc gi Kaposi nhn mnh s khc bit gia LE v lupus vulgaris ( mt th ca lao da). Kaposi (1872) m t 11 trng hp bnh nhn lupus v l ngi u tin a ra thut ng discoid Lupus: lupus dng a. Trong 11 trng hp trn ng nhn thy c 4 bnh nhn c vim phi, au khp, sng hch v a ra nhn xt tn thng ca LE c th chia lm 2 th: th c tn thng da n thun, khu tr, tin trin lnh tnh v th c tn thng da lan ta, km theo tn thng phi hp nhiu c quan : tim, phi, c quan to mu, thn kinh... Cng trong nm 1872, Wiliam osler m t mt trng hp in hnh ca lupus h thng nhng ng t tn l : ban a dng tit dch ( erythema exudativum multiform ). 1908 Kraus v Bohac a ra khi nim lupus cp tnh v lupus mn tnh ni ln s khc bit gia th h thng v th dng a. 1952 Harvey v cng s a ra thut ng: Lupus ban h thng( SLE)9</p> <p>m</p> <p>ngy</p> <p>nay</p> <p>n</p> <p>c</p> <p>chp</p> <p>nhn</p> <p>v</p> <p>s</p> <p>dng</p> <p>rng</p> <p>ri.</p> <p>Vi s pht trin ca cn lm sng, min dch hc, theo thi gian c nhiu tin b t c trong nghin cu, chn on v iu tr SLE. 1948 Hargraves pht hin ra t bo Lupus ( LE cell) trong mu bnh nhn SLE. Sau 1 nm (1949) Haserick tm ra yu t Haserick trong huyt thanh m bn cht l khng th khng nhn (anti nuclear antibody-ANA). 1957 Seligman chng minh trong huyt thanh bnh nhn c yu t phn ng c hiu vi DNA. Tan v cng s (1966) xc nh l khng th khng DNA. Cc pht hin khc: khng th khng histon c ngha trong vic nh hng chn on lupus do thuc, xt nghim min dch huh quang Lupus band test, gip chn on phn bit SLE v DLE... Mi lin quan gia SLE v DLE hin vn cn ang tranh ci. Hai bnh l bin th ca nhau hay l hai th bnh ring bit? Cu tr li cn ng! Dubois theo di 520 trng hp SLE thy c 10,8% tn thng ban u l dng DLE. Ngc li Beck v Rowell (1966) theo di 120 ca DLE trong 5 nm khng thy trng hp no chuyn sang th SLE! V phn loi, hin nay theo cc tc gi M(Dubois) tm chia lm hai th: lupus h thng (SLE). lupus dng a (DLE) v 4 di nhm: Hi chng khng th phospholipid, lupus da bn cp, lupus tr s sinh, lupus su di da.</p> <p>10</p> <p>IV. LM SNGBnh lupus ban h thng (LB) Systemic lupus erythematosus (SLE) c trng bi tn thng vim nhiu t chc, tng t v huyt thanh xut hin cc t khng th khng nhn phn ng vi cc thnh phn khc nhau ca nhn t bo, gi chung l khng th khng nhn (ANA). S hin din ca cc t khng th c hiu lin quan cc c quan tn thng v tin lng ca LB v nhng ri lon t min khc. Cng c nhiu biu hin lm sng, th cng chn on d nhng cng tin lng nng. Ngc li, khi bnh c triu chng n iu hay gi triu chng (pauci-symptom), chn on nghi ng v c th nhm ln sau nhiu thng. Ba biu hin thng gp nht l tn thng khp, da v thn. Cc tiu chun chn on bnh LB c a ra nm 1982 v hon thin nm 1997 bi American College of Rheumatology. Ch cho php chn on chc chn khi c ti thiu 4 tiu chun xut hin. LB xy ra ch yu ph n tr trong la tui 15-40 tui. T l n mc bnh cao gp 10 ln so vi nam, c bit bnh nhn Chu Phi v tin trin thng nng. Ti M tn sut khong 25-50/100.000 dn, cao nht ngi da en l 4/1.000 dn. Cc m hnh thc nghim cho thy cc ni tit sinh dc n steroid c vai tr trong bnh l ny. Vn di truyn c vai tr, cp sinh i cng trng c t l mc bnh l 30%, trong khi cp sinh i khc trng hoc anh ch em rut l 5%. Nhng ngi c allen MHC HLA-B8, HLA-DR2 v HLA-DR3 c nguy c cao mc bnh LB, ngoi ra nhng ngi c thiu ht C4, s11</p> <p>thay i v cu trc th th FcIgG ti t bo ca c quan ch c lin quan vi LB. Bng 1. 11 tiu chun chn on bnh SLE (1982, sa i nm 1997) Ban dng cnh bm mt (malar rash) Ban lupus dng da (discoid rash) Nhy cm nh sng (photosensitivity) Lot ming hay mi hng (oral ulcers) Vim a khp (Arthritis) Vim mng phi hay mng ngoi tim (serositis) Tn thng thn (proliferative lupus nephritis): protein niu &gt; 0,5g/24 gi hay tr niu (renal casts) Tn thng thn kinh (seizures) Ri lon mu: thiu mu tan mu vi HC li tng, gim BC 2,6g/l , nng creatinin mu cao &gt; 124 mmol, thiu mu Hemoglobin&lt; 124g/l, Protein ton phn mu gim. gim tiu cu, khng th khng phospholipid(+).</p> <p>42</p> <p>VIII. IU TRiu tr LB c tnh cht h thng, cn phi kim sot cc t cp ca bnh v c th l ngn chn s ti pht. iu tr c bn bng liu php corticoid, thng dng bng ng ung. Tuy nhin liu php corticoid c th trnh khi tn thng khp t au v t vim. iu tr c th bao gm khng st rt tng hp nh hydroxychloroquin hay chloroquin km theo khng vim khng steroid (aspirin). Cc th da n thun nn s dng corticoid ti ch. Khi LB km theo hi chng vim lan to, mt s ri lon chc nng, l do ca tn thng ph tng th nn s dng liu php corticoid ng ung. Th nh v trung bnh t 0,5 mg prednisolon/kg/ngy. tip theo gim liu dn cho n khi t ngng c hiu qu. Trong trng hp bnh nng c tn thng a ph tng (sinh thit thn) l 1mg prednisolon/kg/ngy. Nu cu thn bnh thng hay lng ng mng y th khng can thip liu php corticoid, vim cu thn tng thu hay cc b th cn iu tr 1mg/kg/ngy, nu vim cu thn tng sinh lan to th cn iu tr 2mg/kg/ngy; 0,5 1 g methylprednisolon tim tnh mch /ngy trong trng hp tin trin nhanh suy thn. Trong trng hp bnh qu nng cn can thip cyclophosphamide, chlorambucil hay azathioprin c th km theo. Cht c ch min dch cho php gim liu corticoid v s dng trong trng hp khng corticoide hay ph thuc corticoid, l ngng trn 10-15mg/ngy i vi bnh nhn c bin chng ring. Tuy nhin theo quan im ca AAAAI th vic phi hp corticoid v cyclophosphamide l liu php iu tr chun vi 750mg/m2/ thng v43</p> <p>ko di trong 6 thng hoc di hn (bolus) v tip theo l 1 bolus/2-3 thng v t nht trong 2 nm Th c triu chng tm thn kinh cn phn bit vi nhim trng, nhim c thuc (liu cao corticoid, khng vim khng steroid), ri lon chuyn ho (ur) hoc bnh l no do tng p hoc ri lon tm thn nguyn pht Cui cng i vi th cp tnh ca vim mch lupus v d bnh lupus thn kinh cp tnh ngi ta phi thm phn huyt tng nhm loi b cc phc hp min dch</p> <p>B-lymphocyte-specific therapeutic targets in SLE. B-lymphocyte depletion (1) rituximab, (2) epratuzumab; reduction of dsDNA titers, (3) LJP 394/abetimus; blockade of T-cell costimulation (4) CTLA4-Ig (abatacept and belatacept), (5) IDEC131 and BG9588; blockade of B-cell stimulation, (6) belimumab.</p> <p>44</p> <p>IX. LUPUS BAN DO THUC.C ch bnh sinh ca LB khng r. Hi chng lupus xut hin sau mt thi gian di dng thuc. Nhiu im cn phn bit lupus do thuc v lupus ban h thng. Lupus do thuc thng lnh tnh, biu hin bi st, vim khp, vim bao hot dch, v ni ban nhng khng c tn thng ph tng (vim thn v h thng thn kinh trung ng him gp). Bnh cnh c th gp do pht hin tnh c khng th khng nhn dng tnh (anti ds DNA m tnh v anti Histon dng tnh). Mt s thuc nh procainamide, hydralazine, isoniazide) Khng th khng nhn hin din thuc khng th anti histon H2A v anti H2B ca lp IgG gp trong lupus do D penicillamid, procainamid, quinidin. Trong lupus do hydralazin khng th antiH3 v H4 n thun khng gn vi DNA Mt khc khng bao gi c anti-DNA chui kp hay anti- Sm trong lupus do thuc tuy nhin anti DNA chui kp lp IgM c th c v b th thng khng gim Mt s thuc c nhc n do kh nng khi ng t tiu t bo v gii phng khng nguyn nhn. Gi thuyt cp nhn nht l kh nng thuc lm thay i cn bng Th1/Th2 theo chiu hng hot ho Th2 v Th2 kch thch t bo lympho B t phn ng vi cc khng nguyn gii phng t hin tng t tiu t bo. Gi thuyt ny c chng minh thm khi iu tr cc anti cytokin c hiu qu bnh nhn LB. Ngoi ra, cc khng th c ch p ng Th1 nh khng th45</p> <p>anti -TNF gy ra hi chng lupus khong 10% bnh nhn. Ngc li ti m IFN- kch thch Th1 d to thun cho bnh Hashimoto, bnh t min m vai tr Th1 chim ch yu. Khng ch c thuc mi gy bnh t min m mt s tc nhn vt l nh tia cc tm cng c th dn n phn ng t min. Hin tng ny gn vi s t tiu t bo ca t bo b do tia cc tm dn n s bc l khng nguyn nhn v p ng t min c trng ca bnh lupus.</p> <p>46</p> <p>X. TI LIU THAM KHO1. Min dch hc c s, Ngc Lin, NXB i Hc Quc Gia H Ni 2. Nguyn Ngc Lanh, Vn nh Hoa (2003). Min dch hc. Trng i hc Y H Ni, Nh xut bn Y hc. 3. Trn Th Minh Dim (2005) Nghin cu khng th antids-DNA v antiENA trong chn on huyt thanh hc bnh lupus ban v bnh x cng b Tp ch Y hc Thc hnh S nm 4. Phm ng Khoa, T Suyoshi, Sugiyama, Takashi yokochi (2003). Tnh a hnh thi ca IL-2 promoteur v th th TNF-II bnh nhn lupt ban , Tp ch Y hc qun s: 323-326 5. Corporaal S, Bijl M, Kallenberg CG (2002). Familial occurrence of autoimmune diseases and autoantibodies in a caucasian population of patients with systemic lupus erythematosus. Clin-Rheumatol. 2002 May, 21(2): 108-113 6. Costa O, Monier JC. (1986) Antihistone antibodies detected by micro ELISA and immunoblotting in mice with lupus like syndrome. Clin. Exp. Immunol, 40: 276-282. 7. Bevra Hannahs Hahn. Systemic lupus erythematosus. Harrisons principles of Internal Medicine. McGraw-Hill; vol 2. 8. Immunology and Cell Biology (2009) 9. http:// www.medicinenet.com/ 10. http://www.nlm.nih.gov/ 11. http://www.nature.com/</p> <p>--------------End-------------47</p> <p>48</p>