NGHIEN Cim KHOA HOC
D A N H G I A TINH HiNH D i u TR| HOI CHdNG STEVENS-JOHNSON VA HOAI T Q T H U O N G Bl N H I I M BQC
TAI KHOA LAM SANG 2, BV DA LI§U, TP, H 6 CHI MINH
Nguyen Trijng Hao*, Huynh Huy Hoang*
i.DAivANDi
Hpi chdng Stevens-Johnson (Stevens- Johnson Syndrome - SJS) va hoai t d t h u p n g bi nhiem ddc (Toxic Epidermal Necrolysis - TEN) la nhdng p h i n d n g thuoe nang nhat""^'. C l SJS va TEN deu dac trUng bdi t l n h trang taeh t h u p n g bi v l Id niem mac, cd nguyen n h i n v l eO che gidng nhau'^', lien quan de'n nhieu loai t h u d c ed n g u y ed phan dng'^'. Su khac nhau chi'nh gida SJS va TEN I I d p nang cua p h i n d n g dua v i o mdc d p lan rdng cua v u n g da bdc tach thUOng bi'^'. Mac dii hiem gap, nhUng 5JS/TEN c d t i c d d n g quan trpng len sdc khde cdng d d n g vl kha nang t d vong cao'^'. T\ le t d v o n g thay ddi d u d i 10% ciia SJS va tren 40% cua TEN, t i le chung cho c l 2 t h e la khoang 20%f-''^l
Tai BV Da lieu TR HCM, b e n h nhan SJS/TEN nhap vien t d 3 n g u d n ehinh: (1) t d cae t i n h chuyenve, (2) t d c l c B V d T P . HCM chuyen de'n, (3) benh n h i n t u d e n .
Trong nhieu n i m qua, khoa Lam sang 2 (BV Da lieu) d l dieu tri cho nhieu benh n h i n bj SJS/
TEN.Tuy nhien, cho den nay, tai BV Da lieu chUa cd nghien edu danh gia viee dieu trj SJS/TEN. Vi vay, chung tdi tien hanh de tai nghien edu n h i m danh g i i ket q u i dieu trj hai hdi chdng tren bang phac d d dieu trj tai khoa Lam sang 2, t d d d
* Benh vien Da hiu Tp Hd Chi Minh.
Phdn biin khoa hgc: PGS. TS Nguyin Hihi Sdu.
rut ra n h d n g bai hpc kinh n g h i e m chia se vdi cac d d n g nghiep t r o n g c u n g n h u ngoai nganh da lieu, giup x d t r i t d t h o n c h o benh nhan SJS/TEN, 11. MUC Tl£U VA P H l / O N G P H A P NGHIEN CU^U
Muc tieu nghien cdu
Khao sat m p t sd d i e d i e m eCia benh nhan SJS/TEN v l ket q u i dieu trj tai khoa L i m sang 2, BV Da lieu.
D o i tUOng nghien cdu
Benh n h i n n h a p vien tai khoa L i m sang 2 vdi chan d o a n hdi c h d n g SJS h o l c T E N t d t h i n g 01 /2009 d e n t h i n g 12/2010.
Phi/ong p h a p nghien cdu
Oay la m p t n g h i e n c d u b i o c l o hang loat ca. Benh n h i n SJS va TEN nhap vien dddc lam benh I n t h e o m a u e h u n g . Nghien cdu vien se d a n h g i i t d n g t r a n g c h u n g cua benh nhan, tim nguyen nhan va g d i b i o cao phan ihig thuoc ( b i o cao ADR).
Tien hanh dieu trj t h e o phac d d ehung cua BV Da lieu TP.HCM:
- Cham sdc tai cho.
- S d d u n g corticoid t r o n g giai doan sdm.
- BCJ nudc, dien g i l i , d a m . - S d d u n g khang sinh thfch h p p . - Hdi chan BS chuyen khoa m a t neu co dau hieu t o n t h u o n g d mat.
ThUc hien e l c xet n g h i e m : Cdng thdc mau, Sinh hda m a u : uree, creatinin, GGT, SGOT, SGPT,
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NGHIEN CUtJ KHOA HOC
ion dd, d u d n g , protein. Cl'y da, cay m i u . Tdng p h i n tich nudc tieu.Chup XQ t i m phdi, d o ECG, sieu I m ndi t a n g (neu can).
Pftdn tieh sdlieu: b i n g phan m e m t h d n g ke E p i - I n f o 2002.
III. K ^ T Q U A NGHIEN c u f u
Cd 17 benh nhan t u o i t r u n g binh 41,2 ( 1 9 - 80 tudi). Oa sd benh n h i n den t d cac t i n h I l n can (12 chiem 70,6%), cdn lai dTRHCM (5 chiem 29,4%).
Ba trudng h p p TEN va 14 t r u d n g hpp SJS duoe ghi n h i n t r o n g n h d m nghien cdu. Chi cd 3 benh nhan (17,6%) cd tien s d d j dng thuoc trudc d i y .
Ve t i c n h i n gay di d n g , da sd khdng biet rd (14 chiem 82,4%), cdn lai I I Carbamazepine (2 chiem 11,8%) va Panadol (1 chiem 5,9%) (xem b i n g 1),
Bdng 1. Cdc thuoe gdy dj dng Thuoc nghi gay
dj iJTng
So trUdng
hop Tile
itong ro - Gi3m dau (dau khdp, dau mat) -Thuoc cam - Ha sot - Thuoc tieu chay
• Khang viem
• Thuoc trj lao - Thuoc tau - Khong ro loat
14 5 2 2 1 1 1 1 1
82,4%
29,4%
11,8%
11,8%
5,9%
5,9%
5,9%
5,9%
5,9%
Carbamazepine
Thdi gian khdi p h i t thay ddi nhieu gida e l c trudng h p p (2 g i d den 1 t h i n g sau khi sd d u n g thudc), vdi trieu chdng khdi p h i t t h u d n g la
ngda, ndi m u n nUdc bdng nude, san d d , cham xuat huyet...
C i c xet nghiem t h u d n g khdng cd nhieu x l o trdn d i n g ke (xem b i n g 2).
Bdng 2. Mpt sd bdt thudng ve xet nghiem
Xet nghiem Sd tru'dng htfp Cong thu'c mau
- Tang bach cau - Tang tieu cau - Giam tieu cau
29,4%
5,9%
5,9%
Men gan - Tang SCOT - Tang SGPT - TangyGT
47,1%
35,3%
23,5%
Ion do - GiamNa^
- GiamCI"
5,9%
23;5%
- Giam Ca**
Tang protein/mau Cay mau, S.aureus +
6 2 1
35,3%
11,8%
5,9%
Cay mCi d da:
- S.aureus + - Pseudomonas aeruginosa +
5,9%
11,8 ChlsdSCORTEN: trung binh l , 4 ( t d 0 - 3 ) , p h l n I n h tien lUpng tUOng ddi tdt eilia nhdng benh nhan trong nhdm nghien cdu (xem b i n g 3).
Bdng 3. ChisdSCORTEN SCORTEN So trudng
htfp Tile
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NGHIEN CLTU KHOA HOC
Ve ket q u i dieu trj, khdng ghi nhan t d v o n g h o l e bien chdng dang ke sau dieu trj.Thdi gian dieu trj t r u n g b i n h cda 3 t r u d n g h p p TEN la 21,7 ngay; trong khi d 14 tru'dng h p p SJS la 13,6 n g i y . IV. B A N L U A N
Tic n h i n g i y d i dng t r o n g nghien cdu cua ehung tdi nhieu nhat la t h u d c g i i m dau (dau khdp, dau mat...), t u y nhien da so khdng duac xac dinh m d t c i c h cu the, rd rang. Chl cd 3 trudng hop xae d i n h ehinh x l c nguyen n h i n (2 Carbamazepine, 1 Panadol). Oieu nay p h i n anh viec sd d u n g thudc khdng kiem soat cua ngUdi dan. Khi cd benh nao d d , hp tU y mua thudc khdng rd loai tai nha t h u d c t i y , den khi bi dj dng rl't khd eho thay t h u d c x l c djnh t i c n h i n g i y SJS/TEN. NgUpe lai, da sd cac nghien cdu tren y van xac djnh dupe t i e nhan g i y dj dng I I k h i n g sinh'^'^' h o l e allopurinol"^l Day la n h d n g nghien cdu d cac nUdc p h i t t n e n m l viee b i n thudc theo toa m d t each chat ehe nen de dang xac d m h t i e n h i n gay dj dng.
Mpt so yeu t d giup tien luong SJS/TEN. Tudi cd t i e ddng quan t r p n g , vdi t l le t d v o n g d tr§ em thap hon so vdi ngudi gia. N h d n g ye'u t d khac cd tien lupng xau la ung t h U kem theo, bien ddi mdt sd gia tri sinh hda (tang d u d n g huyet, t a n g ure va g i i m bicarbonate) d o benh kem theo hay do SJS/TEN. N h d n g yeu t d nay ket h o p vdi nhau tao thanh chi sd SCORTEN d u n g de tien lUOng nguy cO t d v o n g d benh nhan SJS/TEN:
( l ) T u d i > 4 0
(2) Nhjp t i m > 120 Ian/phut (3) Cd su hien dien cua ung t h u (4) Hoai t d t h u p n g bi > 10% ca t h e vao n g i y t h d nhl't
(5) U r e / m l u > 28 m g / d l (10 mmol/1) (6) Glucose > 252 m g / d l (14 mmol/1) (7) Bicarbonate < 20 mEq/l
Mdi ye'u t d tren dupc cho 1 diem. SCORTEN la t d n g sd diem cua 7 yeu t d (diem tdi da la 7),
d i e m sd cang cao t h i k h i nang t d vong cang tang. SCORTENdUpe tfnh t r o n g v d n g 24 gid dau nhap vien va tfnh lai vao ngay t h d ba"*-'^l Nhieu n g h i e n cdu Ong hp k h i n a n g cCia SCORTEN tien d o a n t i le t d v o n g d b e n h n h i n TEN"^. Trong nghien edu eua c h u n g t d i , chl so SCORTEN t u o n g ddi t h a p (0 - 3, t r u n g b i n h 1,4) n^n cac b e n h nhan cd t i e n t u p n g va ket q u i dieu trj tot, C i c n g h i e n c d u t h u c n g h i e m va lam sang eho thay co che cOa SJS/TEN phu thudc vao d a p dng mien djch dac hieu vdi thude. Vi coche mien djch d l dupe n h i c den t d lau, nen nhieu b l c sf d l dieu tri SJS/TEN vdi corticosteroids Ileu cao, m d t sd khac lai sd d u n g t h u d c dc che mien dich n h u c y c l o p h o s p h a m i d e hay cyclosporine.
Vai t r d eCia corticosteroids t r o n g dieu trj SJS/TEN van cdn la van de ban cai, m d t sd bao cao cho r i n g corticosteroids cd hieu q u i tdt'^*"'*' trong khi sd khac lai khuyen nen t r i n h sd dung"'
^°\ Corticosteroids d l dupc sd dung dieu trj TEN t r o n g 30 nam qua. N h d n g t i e gia ung ho nhan m a n h t a m q u a n t r p n g cua viec sd dung corticosteroids sdm d giai doan hdng ban, trong khi phe phan ddi cho r i n g corticosteroids lam g i a t l n g n g u y c d n h i e m t r u n g huyetvltdvong'^', Theo kmh n g h i e m tai BV Da lieu cung nhu ket q u i nghien c d u tren 17 benh nhan, chiing toi nhan thay viec sd d u n g corticosteroids trong giai d o a n sdm cua SJS/TEN g i u p cho ket qua dieu trj t d t h o n .
X d t r i SJS/TEN can c h u y can bang nUdc dien g i l i v l t i n h t r a n g d i n h d u d n g cOa benh nhan, giam dau, dieu tri sdm nhiem t r u n g va cham sde da ki cang. M p t so t i e g i i khuyen c l o nen x d t r i n h d n g trUdng h p p t r o t da nhieu tai dem vj b d n g va dieu t r i k h d n g k h i c gi so vdi benh n h i n b d n g . Tuy n h i e n , k h d n g gidng nhU bong s l u , Idp bi cua b e n h nhan SJS/TEN cdn nguyen ven va q u i t r i n h tai tao t h u p n g bi thudng bat dau t r o n g v d n g 3 de'n 4 ngay'"-^°'. B i e u n i y phu h o p vdi d i e n t i e n phuc hdi d da sd benh nhan
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NGHIEN cufu KHOA HOC
cua ehung tdi. M d t sd t i e g i i lai cho r i n g khdng can thiet p h i i e h i m sde benh n h i n tai ddn vj bdng."«
Nhiem t r u n g huyet va nhiem triJng da la m d t trong nhdng bien chdng chfnh va cd k h i n i n g de dpa mang sdng cua benh nhan. Tic nhan g i y benh t h u d n g la S. aureus va Pseudomonas s p p " " va cung cd t h e I I t u cau khang Methieillin (MRSA), Enterococcus v l Acinetobacter^^^K Trong nghien cdu cua chOng tdi chf cd 1 t r u d n g hpp nhiem t r u n g huyet (chie'm 5,9%) thap hon nhieu so vdi nghien cdu tren 21 benh n h i n TEN d Anh (86%)"^', cd le do khac nhau ve dp nang cua benh.
Ket qua xet nghiem huyet hpc va sinh hda cua benh n h i n t r o n g n h d m nghien cdu eua ehung tdi khdng cd nhieu x l o trdn d i n g ke.
Theo cac nghien edu tren y van, bat t h u d n g huye't hpc t h u d n g gap d benh n h i n TEN. Thieu mau va g i i m lympho I I dau hieu p h d bien, tuy nhien neu cd hien t u o n g d d n g mau ndi mach lan tda v l g i i m bach eau t r u n g tfnh se mang den tien lUpng xau eho benh nhan. €)a sd benh nhan cd hien tUpng ha albumin mau do mat chat t d vung da trcrt. Ngoai ra, he tieu hda cung bj anh hudng vdi t i n g m e n gan t h o a n g qua"^'.
Nghien cdu cilia chung tdi ed m d t sd han che khach quan. Cd mau nhd ed ie do t l le SJS/TEN tai Tp.HCM ndi rieng v l c l e t i n h phfa Nam ndi chung khdng eao. Nghien cdu tren benh n h i n tai khoa L i m sang 2 dieu tri cho nam gidi nen ehua p h i n anh n h d n g d i e trUng ve gidi tfnh cua SJS/TEN, Nghien edu chi tien hanh tren nhdng benh n h i n chUa ed bien chdng nang ne, khdng cd tinh trang ndi khoa kem theo do v l y ket q u i dieu trj t u o n g ddi tdt, chua p h i n I n h d u n g tien lupng nang cCia SJS/TEN.
V. K^T L U A N
Nghien edu da mang lai t d n g quan ve t i n h hinh dieu tri SJS/TEN tai khoa L i m sang 2, BV Da lieu, TR Hd Chf M i n h . Tie n h i n g i y SJS/TEN t h u d n g khdng dupe x l c dinh r d v i benh nhan t u s d d u n g thudc khdng rd loai. Ket qua dieu trj va tien lupng benh nhan t u o n g ddi t d t neu 6dac x d t r f n h a n h c h d n g , kip thdi vdi nhieu bien phap khac nhau tren cO sd phac d d xd trf can ban.
Nen sd d u n g chi sd SCORTEN mdt each t h u d n g quy de danh g i i sdm tien lUpng cCia benh nhan 5JSAEN. Trong thdi gian tdi can cd t h e m nhQng nghien cdu quy m d Idn, mang tfnh t d n g q u i t hon ve nhieu khia canh cua SJS/TEN.
TAI LIEU THAM KHAO
1. Becker DS, Toxic epidermal necrolysis.
Lancet 1998;351:1417-20.
2. Chave TA, M o r t i m e r NJ, Sladden MJ, Hall AP, H u t c h i n s o n PE. Toxic e p i d e r m a l necrolysis: c u r r e n t e v i d e n c e , practical m a n a g e m e n t a n d f u t u r e d i r e c t i o n s . Br J Dermatol 2005; 153:241-53.
3. Sheridan RL, Liu V, A n u p m d i S. Case records o f t h e Massachusetts General Hospital, case 34-2005; a 10-year-old girl w i t h a bullous skin eruption and acute respiratory failure. N Engl J Med 2005;353:2057-66.
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results o f an international prospective study.
Arch Dermatol 2002;138:1019-24.
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1600-7.
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6. Bastuji-Garin S, Rzany B, Stern RS, Shear NH, Naldi L, Roujeau JC. A clinical classification of cases of toxic epidermal necrolysis, Stevens- Johnson syndrome and erythema multiforme.
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8. Chan HL, Stern RS, A r n d t KA et al. The incidence of erythema multiforme, Stevens- Johnson syndrome, and toxic epidermal necrolysis. A population-based study w i t h particular reference t o reactions caused by drugs among outpatients. Arch. Dermatol.
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9. Leenutaphong V, Sivayathorn A, Suthipinittharm P, Sunthonpalin P. Stevens- Johnson syndrome and toxic epidermal necrolysis in Thailand. Int. J. Dermatol. 1993; 32:
4 2 8 - 3 1 .
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Dermatol. 1991; 127:839-42.
11. Wong KC, Kennedy PJ, Lee S. Clinical manifestations and outcomes in 17 cases o f Stevens-Johnson and toxic epidermal necrolysis.
Aust J Dermatol 1999; 40; 131-4.
12. R. Rajaratnam, C. Mann, R Balasubramaniam, J. R. Marsden, S. M. Taibjee, F. Shah, R. Lim, R. Papini, N. M o i e m e n , H. Lewis.
Toxic epidermal necrolysis: retrospective analysis of 21 consecutive cases managed at a tertiary centre. Clinical and Experimental Dermatology 2010; 3 5 : 8 5 3 - 8 6 2 .
13. Halevy S, Ghislain PD, Moekenhaupt M et al. Allopurinol is t h e most c o m m o n cause
o f Stevens-Johnson syndrome and toxic epidermal necrolysis in Europe and Israel. J Am Acad Dermatol 2008; 58; 2 5 - 3 2 .
14. Bastuji-Garin S, Fouchard N, BertocchiM, Roujeau JC, Revuz J, Wolkenstein P. SCORTEN:
a severity-of-i!lness score for toxic epidermal necrolysis. J Invest Dermatol 2000;115:149-53.
15. Guegan S, Bastuji-Garin S, Poszepezynska-Guigne E, Roujeau JC, Revuz J.
Performance o f SCORTEN d u r i n g t h e first five days o f hospitalization t o predict the prognosis of toxic epidermal necrolysis. J Invest Dermatol 2006;126:272-6.
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18. Schneck J, Fagot JP, Sekula P etal. Effects o f treatment o n t h e mortality of Stevens- Johnson syndrome and toxic epidermal necrolysis: a retrospective study on patients included in t h e prospective EuroSCAR study. J A m Acad Dermatol 2008; 58; 33-40.
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Toxic epidermal necrolysis: an analysis of referral patterns and steroid usage. J Burn Care Rehabil 1997;18:520-4.
20. Halebian PH, M a d d e n M a Finkelstein JL er aL Improved b u r n center survival of patients w i t h toxie epidermal necrolysis managed w i t h o u t corticosteroids. A n n Surg 1986/204;
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2 1 . Benh vien Da lieu TRHCM. Phac do dieu trj hdi c h d n g SJS v l TEN 2009.
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