HOl NGH! TOAN QUdC Vg CAC BgNH NHI^M TRCING VA HIWAIDS ii TR6 EM NAM 2013
DAC DIEM LAM S A N G , C A N L A M S A N G V A KET QUA DIEU TRI IMMUNOGLOBULIN BENH TAY C H A N MIENG THE NANG TAI TRUNG T A M N H I KHOA, BENH VIEN TRUNG U-ffNG HUE
T 6 M TAT
Muc tieu: M6 ta dSc diem lam sang, can lam sang va ket qua dieu tri immunoglobuline (IG) benh nhi tay chan ml?ng nSng tai BVTW Hue.
661 tiff ng: 80 benh nhi tay chSn mieng do 2b tn!f len co su' dung IVIG. Nghien cu'u: tien ciHi, tir 12/2011-12/2012. Ket qua vJ ket luan: TCM nang thlTcIng tap trung ci tre < 3 tuoi, nam nhieu hdn nu'. Dau hieu lam sang thu'dng gap ciia benh TCM nang la giat minh, sot, hong ban, mun nUdc/phong nu'dc va loet mieng. Xet nghiem c6 bach cau mau tang; djch nao tuy bleu hien tinh trang viem mang nao ddn nhan. Trieu chu'ng nang thu'dng het sau 40 gid sir dyng IVIG, viec dieu tn MG dung giup cai thien tinh trang benh.
SUMMARY
CLINICAL & PARA-CLINICAL CHARACTERISTICS OF INTRAVENOUS IMMUNOGLOBULIN (IVIG) TREATMENT
FOR CHILDREN WITH SEVERE HAND-FOOT MOUTH DISEASE AT
HUE CENTRAL HOSPITAL Objectives: To describe the clinical, laboratory features and outcome of intravenous immunoglobulin (IVIG) treatment in children v»lth severe hand-foot-mounth disease at Hue Central Hospital. Method: 80 cases with hand-foot and mounth disease from grade 2b who received IVIG. Prospective study, from 12/2011 to 12/2012. Results and conclusions: Severe HFMD cases were mainly In children under 3
* Benh Vi^n Trung Wang HiiS Phdn bl(n klioa lipc: TS. TrSn Thanh Td 42
Tran Kiem Hao*
years old, predominantly In masculine gender.
The common clinical features were myoclonic, febrile, papulovesicular rash/maculop^ular and herpanglna. Laboratory abnormalldes included a raised white cell count; CSF shown the acute aseptic meningitis syndrome. Severe symtoms usually improved and halted at 40 hours alter administered IVIG.
I.OATVXNOI
Benh tay chan mieng (TCM) a Ire em dang la van de sire khde gay quan tam hang dau 6 nhieu nuac tren the giai, dac biet kiiii vuc Dong A va Dong Nam A. Tir nam 2009 den nay benh co xu hirong lien tuc tang va duy tri a muc cao ngay tai mot s6 nuoc c6 nen Icinh te phat trien nhu Nhat Ban, Singapore, Han Quoc...
Tai Viet Nam. b$nh TCM duac ghi nhan tir nam 2003 d tp. H6 Chf Minh. Tir n5ni 2011, benh TCM chinh thuc dirge dua vao he thong bao cao thuong quy theo quy dinh so 48/20I0/TT-BYT, ngay 31/12/2010 cua Bg trucmg Bo Y te.
Nam 2012 ca nuac co 157.6548 benh nhan tay chan mieng; tSng 1,5 l4n so vdi nam 2011. va da co 45 ca tir vong nam 2012 (so vdi 170 ca tir vong 2011) [3], [10].
Dieu trj chua co thudc dac hieu, chi dieu tri h6 trg; viec phat hi?n som, quan ly theo muc do nang cua b^nh va sir dung Immunoglobuline truygn tinh mach (IVIG) gdp phjn lam giam ti le til vong. Tuy vlfj, cac dau hi?u de du bao ca benh nang chita dac hieu, v4n de iiiu tri cSn danh gia hi^u
Y HOC VIET NAM THANG 10 - S6 2/2013
qua lam sang ciia bien phap IVIG, thuoc Milrinone, Magne Sulphate,...[10].
Nham gop phan nang cao chat lugng chan doan va dieu tri benh TCM, chung toi thuc hien nghien cuu nay voi 2 muc tieu:
Xdc dinh dgc diem lam sdng. can Idm sdng cua binh TCM the ndng.
Ddnh gid ket qud cua IVIG trong dieu tri benh TCM the ndng.
II. OOI TirONG VA PHirONG PHAP NGHIEN COU Doi tugng nghi£n cuu: Tat ca b?nh nhi dugc chan doan TCM d\ra vao lam sang, djch te hoc va can lam sang, phan dp tir 2b nhom 2 tro len va dugc chi dinh dieu trj truyen IVIG (Pentaglobin'^) tai Trung tam Nhi khoa BVTWHul
Tieu chuan chan doan, dieu tri b?nh TCM dv;a theo QuySt djnh s6 2554 /QD-BYT (2011) va s6 1003/QD-BYT (2012) ciia Bo trucmgBo Yt^fl].
Chgn mau theo phuoTig phap thuan tien.
Thai gian tir 12/2011 den 12/2012.
Phuong phap nghien ciiu: mo ta, can thiep lam sang, khong co nhom doi chung.
Xu ly s6 li?u bang phdn mdm SPSS 15.
III. K^QUAVA BAN LUAN
Tir thang 12/2011 din thang 12/2012 co 80 tre nhap vien dugc xac dinh chan doan benh TCM nang va dugc dieu tri hkng IVIG.
3.1. D^c diim mau nghien cihi
Biiu dd 1: Phdn bo b?nh TCM theo cdc muc dp n^ng •
Dac diem theo phan dp: TCM dp 2b nhom 2 chi6m 30/80 = 37,5% va dp 3 chiim 48/80 = 60%; 2/80 = 2,5% la do 4. Tai BV Nhi Dong 2, trong so TCM tir dg 2b tra len phai nhap vien thi dp 2b chiem nhieu nhat, sau do la dp 3 va do 4, vai ti le phan tram lan lugt la 57%, 36% va 7% [3]. Chung toi gap dp 3 nhidu hem, co the do dac diem benh thay doi theo dia phuang va co the do benh nhi dk\ mupn, khi benh da n^ng.
Phan bo theo dja phuang: chii yeu la benh nhi tir tuyan huyen 42/80 = 52,5%;
thanh ph6 10/80 = 12,5% va ngoai tinh 28/80
= 35%. Tai phia Nam, benh thuang tap trung o nhung nai c6 m^t dp dan cu dong due. So dT chung toi gap nhieu tir tuyen huyen co the do cac 6 djch xuat phat tir nhung nai nay, va chua CO bien phap khong che djch lay lan.
Phan b6 theo giai: nam 44/80 = 55% va nu 36/80 - 45%: ti le nam/niJ = 1.2. Cac nghien cuu tai cac dja phuong cung co nhan dinh nam gap nhieu ban nil. Tai Dai Loan, Singapore, Malaysia cung ghi nhan su uu the nay vai ti le tir 1,5/1 den 2.5/1 [6]. Chua co y van giai thich tinh trang benh nSng lien quan den gioi tinh, nhung su khac biet nay co the gop phan giiip tim cac yeu to lien quan den muc dp nang ciia benh.
Lua tuoi gap nhieu nhdt 1- 3 tu6i (54/80=67,5%). day la dp tu6i tre dugc giii di hpc nha tre va co nhieu nguy co tiep xtic vai nguon benh; tiep den la liia tuoi < 12 thang (18/80 = 22,5%), khong gap truang hop nao tren 5 tuoi. Theo y van. TCM gap chii yeu a tre < 5 tuoi, nhat la a tre < 3 tu6i. Mpt s6 nghien ciiu 6 Dai loan cho thdy tre < 3 tu6i CO nguy CO bien chiing cao hon. Nghien ciiu tai BV Nhi ddng 2, hon 90% tre TCM dp 2b trof len nam trong dp 1-3 tuoi [2], [3].
HOI NGH! TOAN QUgC \li CAC BgNH NHI^M TRONG VA HIV/AIDS 6 TRg EM NAM 2013
3.2. D9c diim lam sang
Thcri dijm tr6 nh^p vi$n: chii yeu vao ngay thir 2-3 ciia benh, chiem li 1^ 52,5%
(42/80), sdm nhSt 1 ngay (25%) vd mugn nhat la 6 ngay. Dieu nay phii hgp y vSn, cung nhu mpt so nghien ciru khde, cdc bien chirng ciia benh thirdng xay ra tir ngdy thir 2-5 cua benh. Tai BV Nhi TW, tinh trying nang
thuimg xuit hien vao ngay thu 3 (42,9%) v4 Ihir 4 (33,8%) cua benh. T^i BVND 2, ghi nhan da so trircmg hgp ndng dugc nhap vien vao ngdy thir 2-3 ciia benh, trong dd cac trucmg hop ndng dp 3-4 Iai cd thdi diem nhSp vien sdm hon so vdi nhdm 2b [2] [3] [10], Bdng 3.1: Cdc tripu chung trong qua trinh nhap vien
Tri^u chii'ng Sot
Lo^t mi?ng Hong ban
Mun nucjc, phong nude Hodng hot, choi vai Giat minh Co giat That dieu Rdi loan tri giac
n 68 54 68 60 34 78 6 24 6
Ti le (%) 85 70 85 75 42,5 97,5 7,5 30 7.5 Trong nghien cim ndy, bieu hien lam
sang thucmg gap ciia benh TCM nang la giat minh (97.5%), s6t (85%). hdng ban (85%).
mun nudc/phdng nude (75%i) vd loet mieng (70%). Ket qua nay ciing phii hgp vdi cdc nghien cuu trong nuac. Tai BV Nhi TU', BV DK Tien Giang. tri^u chimg hay gap doi vdi the nang la mach nhanh, roi loan y thirc, HA tdng, khd tho, run chi va co giat [5], [10].
BVND 2 ghi nhdn dau hieu hong ban, loet mieng va sot la nhQ'ng bieu hien chii yeu ciia b?nh d cdc dp ndng [3].
Dau hieu sdl chiem 85% (68/80). Phan Idn sdt < 39°C. chidm 60% (48/80). Sot cao>
39"C chi6m 25% (20/80). Truang Thi Chigl Ngu ghi nhan hau hjt cac trudng hgp TCM cd bien chimg deu cd sot [4]. Diju nay cung tuong III cdc tac gia nude ngoai, Chang va cdng sir ghi nhan sdt > 39°C va keo dai > 3 ngay c6 y nghTa tien lugng biSn chiing thSn kinh [6]. Sdt cao vd keo dai cd le do dap img viem manh vdi viec phdng thich qua mire cac cytokine, mpt sd it la do tdn thucmg TKTW lien quan den trung tam dieu nhiet trong cac trudng hgp ton thuang than nao nang [7], [9].
Bang 3.2: Tinh chat phat ban/phdng nude d da Vi tri
Long bdn tay Gdi Mong Long ban chan
n 68 12 18 76
Ti le (%) 85 15 22,5
95
Y HQC VigT NAM THANG 10 - SO 2/2013
Tinh chat phM ban/ phong nuoc cf da: Vi tri chiem ty le cao nhat la long ban chan (95%) va long ban tay (85%). Theo Peter C.
McMirm, tre nhilm EV71 thuang bieu hien sang thuong da hong ban, con Coxackie sang thuong dang phong nuoc [8]. Do benh nhi bj TCM trong nghien ciiu cua chung toi la nang, CO kha nang bi nhiem EV 71 nhieu hon nen ti le hong ban nhieu ban phong nuoc.
Giat minh dugc ghi nhan 78 truang hgp (97,5%), tuong tu cac tac gi^ nuac ngoai.
Theo Chang va cong sy:: rung giat co gap trong benh canh t6n viem mang nao vo triing va viem nao do EV71. Theo Hsiao-Kuo-Lu rung giat ca co lien quan vai tac nhan EV71.
Giat minh va rung giat co la do kich thich tir vo nao, than nao. tieu nao va tiiy s6ng trong benhlydoEV71 [6].
3.3. Bien chirng cua benh
Bdng 3.3: Mpt so bien chiing thirang g5p Bien chirng
Than kinh Tuan hoan Hdhap Tdng
n 52 58 54 80
Ti 1? (%) 65 72,5 67,5 95 Bien chung than kinh chiem 65%, ghi
nhan viem mang nao hay gap nhat, tuong tu cac nghien ciiu trong va ngoai nuac khac.
Bi8n chiing tuSn hoan (nhip tim nhanh, tang huy6t ap) chiem 72,5%; ho hap (roi lo^n nhip tho) 67,5%. Cac dau hieu nay bieu hien tinh trang roi loan he than kinh tu dpng, chiing dugc tao nen bai vai tro ciia dap iing viem ciia cytokin, do phong thich qua miic cac catecholamin, ciing nhu tac dpng true tiep
3.4. Dac diem can lam sang
Bang 3.4: Cong thiic mau liic nhap vien
den trung tam tuan hoan. ho hap 6 than nao;
trong d6 t6n thuang som than nao voi bieu hien giat minh, run loang choang la nhung dSu hieu som va xay ra vai tan suat cao a cac benh nhan tii' dp 2b tra len [7].
Theo Pham Nhat An. bien chirng hay gap nhu viem co tim. phii phoi cap. soc. viem nao mang nao, va tren mpt benh nhan co the co nhieu bien chiing [10].
Cong thu'c mau H6ngcau(x lO'/ml) Hb(g/dl) Bach cdu (x 10''/ml) Ti6ucau(x lOVml)
Thap nhat 3,65
9 6,25
175
Cao nhat 6,10
18 20,9 543
Trung binh ± SD 4,47±0,47 11.10±1,63 12,18±3.66 323,68±105,47 Ket qua cong thiic mau liic nhap vien cho
thay CO su tang bach eau, va tieu cau. hong ckx va Hb trong bien doi. CRP cung trong gioi ban binh thuang. Nghien cim ciia Truong Thj Chiet Ngu. so lugng BC trung binh 12.600/mm^, s6 lugng TC trung binh la 327.000/mm^ [4]. Nghien ciiu cua cac tac gja nuac ngoai, BC tang la yeu to nguy co bien chiing suy tuan hoan ho hap.
Tai BV Nhi TW ti le bach cau mau tSng
doi vai TCM do 2b 32.3%: do 3 29.8%; do 4 la 48.6% va ti le CRP tang ISn luat la 36.5%;
34,9%; 59,4% theo thir tu. Tai BVND 2. BC mau CO xu huqng tang theo miic dp benh, trong khi ti^u cau, CRP khong bi^n doi [10].
Theo lac gia Do Quang Thanh, cac xet nghiem thuong qui nhu bach cau_ mau, dextrotix^ va CRP chua goi y co moi lien quan nhieu vai benh tay chan mieng [5],
HO: NGHI TOAN QU6C Vg CAC BgNH NH|£M TRONG VA HIWAIDS d IRt EM NAM 2013
Bing 3.S: Ddc di6m Sinh hda mdu Sinh hda mdu
Glucose mau (mmol/1) Lactate
Thap nhat"
1,7 0,9
< 0,003
Cao nh^t 11,0 3,5 0,026
Trung binh ± SD 4,79±1,96 1,88±0,91 0.005±0,003 Iroponin I ^ u,uuj i u,uzu i v,uu.j^v,v.u.; j Cdc xdt nghi?m sinh hda mdu trong gidi han binh thudng. Theo cac chuyen gia ciia 16 chirc Y tS The gidi, cdc ySu t6 c^i lang sdng tien lugng bSnh nang va lien quan den tit vong gom: bach cau mdu > 16.000/mm^, tieu cdu > 400.000/mm\ dudng mau > 180 mm%, ySu t6 c^i lang sdng tien lugng bSnh nang va lien quan den tit vong
^^^ 1^^,.,. ...f^.. ... ...J > l6.000/mn?.tKU oka > 40Cl.00()/mm\i\lc lactate mdu > 5 mmol/L, toan chuyin hda ndng va Troponin I (-I-) [10].
Bang 3.6: Djic diem Djch ndo tuy Djch nSo tiiy Ta bao BC (/mm") Protid Glucose
Thap nh^t 2 0,15
3,0
Cao nhat 650 1,80 6,5
Trung binh ± SD 96,6±14,2 0,53±0,37 4,08±0,82 Trong 80 tre dugc chpc dich ndp tuy 52 tre
biiu hien cua benh canh mdng ndo sieu vi (tdng bach cdu, cao nhdt Id 650 BC/ram-"). Protid va glucose DNT binh thudng. Tai BVND 2 ghi nhdn tat cd cac trucmg hgp dugc chpc do tiiy sdng deu cd tinh trang thay ddi te bao voi tang bach cdu don nhdn trong DNT [3]. Dieu nay phu hgp vdi y van, EV71 thudng gay tinh trang viem mang nao dan nhdn [7].
Chan doan huyet thanh hpc virus EV71:
IgM (-^) chiem 64/80 = 80%. T?ii nude ta (2012) theo bdo cao cua Bp Y tl, ti le EV71 (+) chiem 64.5% cac mdu virus EV duong tinh gay benh TCM. Cdc vu dich tai Dai Loan, Singapore. Indonesia ciing ghi nh^
cac trudng hgp benh TCM ndng c6 ton thucmg nao. tim phdi, tac nhdn phan lap duoc chu yiu Id EV71. Dieu nay rat quan trpng 4e cd thi kit luan EV71 la tdc nhan gay bien chung nang trong benh TCM [6], [7], [8], [9].
3.5. Ket qua dieu tri Immunoglobulin tinh mach
Hdu hit benh nhi dugc sir dung IVIG trong 2 ngdy lien tilp (78/80 = 97,5%). Ghi nhan tai BVND 2, ti Ie dimg 2 lilu IVIG chiim mpt nira cac trudng hgp dp 2b vd hau het cac trudng hpp dp 3-4 [2], [3]. Cac tac gia Dai Loan kit hgp IVIG va van mach Milrinone sdm nhSm dieu hda cytokine dugc kich hoat trong qud trinh benh da han che dugc dien tien nang tai mot sd thdi diem ciia benh [9].
Thoi gian het tr/c (gifr) Sot
Bat thudngTKTW Rdi loan hd hap Roi loan tuan hoan
Thap nhat 3 0 4 4
Cao nhat 82 58 90 72
Trung binh ± SD 39,9 ±18,3 16,49 ±15,88
28,5 ±16,6 30,35 ±17,15 Phan Idn cdc trudng hgp het trieu chimg
sau 40 gid sir dyng IVIG, sdm nhdt ngay khi diing xong IG lilu thir nhdt, cham nhdt sau 90 gid. Trieu chimg TKTW cdi thien nhanh nhat, trung binh sau truyin 16,5 gid; tilp din Id cdc rdi loan hd hdp (28,5 gid), tudn hoan 46
(30,3 gid). Rieng dau hieu sdt cdi thien muon hem, khoang 40 gia.
Tai BV Benh Nhiet ddi tp. Hd Chi Minh (2011), ghi nhdn tren 194 benh nhi ndng ilp 2b vd 3 dugc sir dung IVIG, vdn cd 13,4%
benh nhdn chuyen dp ndng hon sau dung
Y HOC VIET NAM T H A N G 1 0 - 3 0 2/2013
IVIG va da so la tir 2b chuyen sang do 3 [3].
Van de nghien ciiu hieu qua cua IVIG tren lam sang con rat hiem, chua c6 mgt thir nghiem lam sang nao. Cac tac gia sii dung dua trSn kinh nghiem la chinh v^ dua vao co chS: trung hoa virus ciia IVIG, anh huong len san xuat cytokine a lympho T v^
monocyte/macrophages, ma vai tro cua cytokine trong co che b?nh sinh cua TCM co bien chiing da duoc nhin nhan [7].
Tac gia Wang S va c^ng sy cho thdy co s\r giam co y nghia thong ke nong d§ IFN- gamma, IL-6, IL-8, IL-10, and IL-13 trong huyet thanh cua benh nhi TCM bj phu ph6i c4p va IL-6, IL-8 6 b^nh nhi TCM co bieu hi?n roi loan he than kinh tir dong sau dieu tri IVIG, tir do tac gia ket luan IVIG co vai tro trong dieu tri TCM co bien chung viem than n3o, tae gia ciing de nghi can co thOc nghiem 1dm sang de kiem chiing gia thuyet nay [9].
78 b?nh nhi h6i ph\ic hoan toan, co 1 truang hap dl chung than kinh trung uang va h6 hSp {h6n me va tha may keo dai), khong CO tir vong. Phan lan benh nhi TCM nang dugc di6u hi tai PICU tir 24-72 gia {30/40 = 75%). Nhin chung vi?c diiu tri IVIG cho k^t qua tot, neu chi dinh kip thai, b?nh nhi khoi b?nh ma khong de l^i di chiing. Nhijug truang hap da vao suy tuan hoan ho hap thi khong hieu qua, b?nh nhi vin tir vong, hoac d^ di chiing nang. Bo Y te khuyen cao khong s^ dung IVIG cho benh nhi TCM dp 4.
IV. KET LU^ti
TCM nang thudng t|ip trung a tre < 3 tuoi.
Trieu chiing Iam sang tiiuong ggp cua benh TCM n^ng la giat minh, s6t, hflng ban, mun nuoc/phong nuac va loet mi^ng. Xet nghiem CO bgch cau mau tang; djch n5o tuy bieu hi|n tinh trang viem mang nao dan nhan.
Trieu chiing nang thuang hk sau 40 gia sur dyng IVIG, nhanh nhSt ngay khi dung xong IG lieu thii nhit, cham nh^t sau 90 gid.
Viec dieu tri IVIG kip thdi, dung thdi diem va miic do nang giup cai thien lam sang va can lam sang ciia benh.
TAIU^UTHAMKHAO
1. Bo Y T ^ (2011, 2012), Hu'dng d i n chin doan va diSu tri benh tay chan mi?ng, Quyet djnh so 2554 / Q D - B Y T va 1003/QD-BYT cua Bp trirdng Bo Y te
2. Che T h a n h D o a n , T r a n T h j V i ^ t , D S Chau V i ^ t , T r a n T h j T h u y (2008), "Dac di6m lam sang, c^n lam sang va kk qua dieu trj IG tren b?nh nhan T C M n§ng t^i khoa N h i l m B V N D 2", Y Hpc t p . H C M , 12(4), tr 24-30 3. Cue q u ^ n l^' KhAm chu-a bSnh (201 l),"Tai
li?ii hoi nghi chia se kinh nghiem chan doan, di6u trj b?nh tay chan mi?ng", tp. H C M 27/12/2011.
4. T r u o n g T h i Chiet Ngir (2008). "Dac d i i m benh tay chan mieng d tre nhap vien tai B V N D 1 " , Luan v5n tot nghi?p npi tru b?nh vien chuyen nganh N h i .
5. Do Quang T h a n h , Ta V a n T r a m (2011).
"Dac diem djch t l , lam sang, can lam sang va d i i u trj benh tay chan mieng tai benh vien da khoa Tien giang", Y hpc tp. H6 Chi M i n h , tap 15, so 4.
6. Chan K w a i Peng et a l . (2003), "Epidemic hand, foot, mouth disease caused by human enterovirus 7 1 , Singapore". Emerging Infectious Disease. 9(1); pp.78-85.
7. L i n Tzou-Yien et al. (2003)
"Proinflammatory cytokine reactions in Enterovirus 71 infections o f the central nervous system" Clinical Infectious Diseases, 36: 269-274.
8. Peter C. M c M i n n (2002), " A n overview o f the evolution o f Enterovirus 71 and its clinical and public health significance", FEMS Microbiology Reviews, 26: 91-107.
9. W a n g S e t a l . (2006), "Modulation o f cytokine production by I V I G in patients with enterovirus 71 associated brainstem encephalitis". J Clin V i r o l . Sep; 37(l):47-52.
10. W H O (2013). "Workshop on hand foot and mouth disease", Hanoi. Vietnam, 04-05 A p r i l .
