TAP CHi Y DUOC L A M S A N G 108 Tap 12 - Sd 8/2017
Dac diem lam sang va cac roi loan mien dich cua benh nhan lupus ban do he thong tien trien muc do nang
Clinical manifestations and immune disorders in the patients with severe flare systemic lupus erythematosus
Huynh Van Khoa , hi Anh Thy , Le Thu Ha *Benh vien ChgRay,
**Benh vien Trung uong Qudn ddi 108
Muc tiiu: Nghien cdu dac diem lam sang, can lam sang, mpt sd yeu to mien dich, ndng do mdt sd cytokine lupus ban dd he thdng (systemic lupus erythematosus - SLE) co dot tien trien nang. Ddi tUOng vd phuang phdp: 112 benh nhan lupus ban do he thdng dupc chan doan theo tieu chuan Hoi Thap khdp Hoa Ky- 1997va cd dot tien trien nang tai Benhvien Cho Ray tU thang 5/2011 den thang 12/2015. Tat ca cac benh nhan deu dUoc kham theo mau benh an thdng nhat. Kitqud: Ngoai cac bieu hien lam sang d da, niem mac, khdp; cdn cd cac bieu hien khac: Loan than chiem ty le 20,5%, co giat 15,2%, phii 34,8%, tang huyet ap 13,4%, viem mach 6,3%. Co 80,4% benh nhan cd rdi loan ve huyet hoc, tdn thUOng than 76,8%, tdn thuang than kinh trung Udng 28,6%, tran djch mang phdi 50,9%, tran djch mang tim 25%, tang men co 16,1%, tang men gan 25%. Tang cholesterol mau chiem ty le 66,7%, tang triglycerid 87,9%, giam HDL- cholesterol 56,6%, tang LDL- cholesterol 44,9%. Ty le ANA (+) gap 98,2%, anti-dsDNA (+) gap 79,5%, anti-Sm gap 42,7%, anti-cardiolipine IgM (+) 6,8%, anti-cardiolipine IgG (+) 27,2%, anti-Ro (+) 51%, anti-La (+) 13%. Ndng dp C3 giam chiem ty le 94,6%, giam C4 la 63,4%, tang IgA chiem t:i' le 8,3%, tang IgE 80%, tang IgG 25,7%, tang IgM ia 9,2%. TNFA tang chiem ty le 40,4%, 1L6 tang 95,7% va ILIO tang 85,^%. Kit ludn: d benh nhan SLE co dpt tien trien nang, tdn thuong cac noi tang nhU huyet hpc, than, than kinh trung UPng, tim, phdi la rat thudng gap. T^ le benh nhan bi rdi loan lipid mau va tang cac cytokine TNFA, IL6, ILl 0 la rat cao.
Tdkhda: Lam sang, can lam sang, rdi loan mien dich, lupus ban do nang.
Summary
Objective: To access clinical manifestations and some immune disorders in serum in patient with severe flare systemic lupus erythematosus (SLE). Subject and method: 112 patients at the Cho Ray Hospital were diagnosed SLE by criteria of ACR - 1997 with severe flare from May 2011 to December 2015. All patients were examined following a pattern of medical record, fiesu/f: Clinical manifestations were expressed popularly in the skin, mucosa, joints, and there were scare some other organs such as psychosis accounted for 20.5%, convulsions 15.2%, edema 34.8%, hypertention 13.4%, systemic vasculitis 6.3%. 80.4% o f t h e patients had hematological disorders, 76.8% lupus nephritis, 28.6% central nervous system (CNS), 50.9% pleural effusion, 25% pericardial effusion, 16.1% increase muscle enzyme.
Ngdy nhdn bdi- 21/9/2017. ngdy chap nhdn dang. 29/9/2017
Nguai phdn hoi. Huynh Vdn Khoa, Email: khoa-hv@yahoo com - B^nh vi^n ChoRdy
JOURNAL OF 108 - CLINICAL fWlEDICINE AND PHARMACY Vol.12-N''8/2017
25% increase in liver enzymes. High cholesterol levels were 66.7%, triglycerides 87.9%, decreased HDL cholesterol 56.6%, and increased LDL cholesterol 44.9%. The rate of positive ANA and anti-dsDNA were particularly 98.2% and 79.5%. Anti-Sm (-^) 42.7%, anti-cardiolipine IgM (+) 6.8%, anti-cardiolipine IgG (+) 27.2%, anti-Ro (+) 51%, anti-La (-I-) 13%. C3 decreased 94.6%, C4 decreased 63.4%; IgA increased 8.3%, IgE Increased 80%, increased IgG 25.7%, Increased IgM 9.2%. TNFA increased 40.4%, IL6 increased 95.7%
and ILIO increased 85.1%. Conclusion: In severe SLE, damage of some organs such as hematology, kidney. Central nervous system, heart, lung was popular. The rate of hyperlipidemia and the increase of TNFA, IL6 and ILl 0 level in serum were also high.
Keywords: Clinical manifestation, subclinical, immune disorder, severe systemic lupus erythematosus.
1 . fiat van cle
Lupus ban dd he thdng (systemic lupus erythematosus - SLE) la mdt benh man tfnh do rdi loan dieu hda cua he thdng mi^n dich. Bieu hien lam sang eae dpt tien trien cua benh thudng 6 da, khdp, huyet hpc, tdn thuong cac cd quan ndi tang (than, tim mach, hd h^p...) [1]. Cac xet nghiem can lam sang va cac rdi loan mi^n djch cung rat da dang va phong phu tuy theo ddt tien trien nang cua benh.
Chung tdi tien hanh nghidn cdu nay vdi muc tieu:
Ddnh gid dgc diim Idm sdng vd cdc rdi logn mien djch dbinh nhdn SLE cd dat tien trien ndng.
2. Doi tUdng va phUtfng phap
2.1. Ddi tugng: Nghien cdu thUc hien tai Khoa Npi Co XUdng Khdp, Benh vien Chd Ray, Thanh phd Hd Chf Minh t d thang 5/2011 den thang 12/2015 tren 112 benh nhan (BN) SLE dUpc chan doan theo tieu ehuan Hdi Thap khdp My nam 1997. Xae dinh cd deft tien trien nang cda benh khi thang d i i m SLEDAI > 12
diem va cd it nhat cd mdt trong cac tdn thuong noi tang nang (gdm viem than lupus cd hdi chiifng than hu, ton thuong than kinh trung Udng, thieu mau tan huyet nang, xuat huyet phdi, viem co tim) [11],
2.2. Phuang phdp: Md ta, eat ngang. XCf ly so lieu: Bang phan mem SPSS 18.0. Bien dinh tinh mo ta bSng tan suat, tJ- le (Chl-square test). Bien djnh lUdng bieu dien X + SD (t - test) hay trung vi, Idn - nhd nhat (test Mann-Whitney). So sanh cd •y nghla thdng ke khi p<0,05.
3. Ket qua
3.1. Dgc diem nhdm binh nhdn nghiin cdu:
Lda tudi mac benh cao nhat tap trung d tudi 20 - 29 tudi chiem t;y' le 45,5%, tinh ehung cho Ida tudi xii 20 - 39 tudi ehiem ty le 68,2%. Ty le benh nhan (BN) nC chiem 90,2%, nam gidi 9,8%. Thdi gian mae benh chu yeu < 3 nam chiem X^ le 77,7%, > 3 nam chiem ty le 22,3%, thdi gian mac benh trung binh la 21,63 ± 30,37 thang.
3.2. Ddc diem Idm sdng
BSng 1. Mpt sd trieu chufng lam sang (n = 112) TT
1 2 3 4 5 6 7 8 9 10
Trieu chu^g Co giat
Loan than Hoi chiing nao liGru co Oau dau Lupus Tai bien mach nao Viem mach Viem l<hdp Dau (viem co) Ban m6i xuat hien Rung toe
SoBN 17 23 13 8 2 7 74 12 69 55
T J I e % 15,2 20,5 11,6 7,1 1,8 6,3 66,1 10,7 61,6 49,1
TAP CHl Y DUOC LAIVI SANG 108 Tap 12-So 8/2017
Bang 1 . Mot so trieu chiiifng lam sang (n = 112) (tiep theo) TT
11 12 13 14
Trieu Chiang Loet mieng
PhCi Sdt Tang huyet ap
SoBN 29 39 33 15
T 9 l e % 25,9 34,8 29,5 13,4 Nhdn xit: Bieu hien lam sang thudng gap d da, niem mac, khdp. Bieu hien hiem gap hon: Loan than chiem ty Id 20,5%, co giat 15,2%, phu 34,8%, tang huyet ap 13,4%, viem mach 6,3%.
3.3. Dgc diem can Idm sang 3.3.1. Ddc diim cdc chisd huyet hgc
Bang 2. Dac diem cac chi sd huyet hoc (n = 112) Cac chi so
GiSm huyet sac to Gi3m bach cau GiSm tieu c l u
Tang mau l i n g (gid dau) > 10mm
seiBN 85 21 29 98
T y l e % 75,9 18,8 25,9 87,5 Nhdn xit: Jy leeao benh nhan ed thieu mau 75% va tang mau lang gid dau 87,5%. Ty le giam bach cau va tieu eau gap thap hon tUdng dng la 28,8% va 25,9%.
3.3.2. Ddc diem cdc chisd sinh hda mdu
Bang 3. fiac diem cac chi so sinh hoa mau (n = 112) chisd
GiSm protein (g/dl) < 6 GiSm albumin (g/dl) < 3,5 Tang CRP mau (mg/l) > 6 eGFR giiim < 60mi/ph Tang ALT (GPT) > 50 Tang AST (GOT) a 50 Tang CPK > 200 Tang LDH 2 400
SoBN 78 92 18 26 28 54 18 77
T > l e % 69,6 92,1 16,1 23,2 25,0 48,2 16,1 68,8
Nhdn xit: Ty le giam protid va albumin mau cao 69,6% va 92,1%. Ty le suy giam chdc nang than gap d 23,2% bdnh nhan.
3.3.3. Dgcdiem ch! sd lipid mdu
BSng 4. fiac cTiem chi sd lipid mau chisd
Tang cholesterol Tang triglycerides Gi^m HDL -choiesterol Tang LDL-cholesterol
Sd BN (n = 99) 66 87 56 40
T J I c % 66,7 87,9 56,6 44,9
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY
Nhdn xet: Rdi loan lipid mau rat thudng gap trong dd gap nhieu nh^t la tang triglyceride 87,9 cholesterol mau chiem 66,7%, giSm HDL - cholesterol 56,6%, tang LDL - cholesterol 44,9%.
•. tang
3.3.4. Ddc diim nddc tieu
BSng 5. Dac diem nUdc tieu ( n = 112) Dac diem
Protein nieu (+) Protein nieu > 0,5g/24 gid Protein nieu >= 3,5g/24 gid
Hong cau (+) Bach cau (+)
Protein nieu 24 gid (g) trung blnh
SdBN 106
86 56 90 17
T y l e % 94,6 76,8 50 80,4 15,2 5,61 ±4,95
Nhdn xit: Ty le BN cd protein nieu chiem 94,6%, protein nieu/24 gid > 0,5g chiem 76,8%, protein nieu/24 gid > 3,5g ehiem 50%. Bdnh nhan cd hdng cau nidu cung gap vdi X^ le cao 80,4%.
3.3.5. Ddc diem tdn thdOng ca quan dich
Bang 6. Phan chia theo cac ccrquan cd tdn thUtfng (n = 112) Coquan
Khdp Da - niem mac Than Than kinh Gan
Phoi (tran djch mang phdi) Tim (tran djch mang tim) Tieu hoa
Huyet hpc
SdBN 74 78 86 32 28 57 28 11 90
T y l e % 66,1 69,6 76,8 28,6 25,0 50,9 25,0 9,8 80,4 Nhdn xit: Ty le cd tdn thUdng khdp chiem 66,1 % va da-niem mac la 69,6%. Cac tdn thuong ndi tang khac nhu tdn thUdng than 76,8%, than kinh trung Udng 28,6%, tang men gan 25%, hd hap 50,9%, tim mach 25%, tieu hda 9,8%, huyet hpc 80,4%.
3.3.6. Ddc diem khdng the tdmien
BSng 7. fiac diem mot so khang the tU mien Khang the tif mien (+)
ANA Anti-ds DNA Anti-Sm(n = 103) Anti-cardiolipin igM (n = 103) Anti-cardiolipin igG (n = 103) Anti-SSA(Ro)(n=102) Anti-SSB(La)(n=100)
SdBN 110 89 44 7 28 52 13
TJIc%
98,2 79,5 42,7 6,8 27,2 51,0 13,0
TAP CHl Y DJOC LAM SANG 1 Tap 12-So 8/2017
Nhdn xet: Ty le ANA (+) gap 98,2%, anti-dsDNA{-i-) gap 79,5%, anti-Sm gap 42,7%, anti-cardiolipine IgM (-I-) 6,8%, anti-cardiolipine IgG (-I-) 27,2%, anti-Ro (-F) 51 %, anti-La (+) 13%.
3.3.7. Dgc diem nong do cdc bo the, immunoglobulin mien dich
Bang 8. fiac diem nong do cac b6 the, immunoglobulin mien djch Chisd
C3giSm(n = 112) C4giSm(n=112) IgA tang ( n = 109) igEtang(n = 95) igG tang (n = 109) igMtang(n=109)
SdBN 106
71 9 76 28 10
TJIe%
94,6 63,4 8,3 80,0 25,7 9,2 Nhdn xet: Ndng dd C3 giam chiem ty le 94,6%, giam C4 la 63,4%, tang IgE 80%.
3.3.8. Dgc diem ndng do cdc cytokine
Bang 9. fiac diem ndng dd mot so' cytokine (n = 94) Chisd
Tang TNFA Tang iL6 Tang iLlO
SdBN 38 90 80
T y l e % 40,4 95,7 85,1 Nhdnxit: Ndng do TNFA tang ehiem ty le 40,4%, 1L6 tang 95,7% va ILIO tang 85,6^^^
4.1. Ogc diem chung cua nhdm nghien cdu Tuoi trung binh cua nhdm nghien cdu la 25,65 ± 7,71, IUa tudi mac benh chu yeu la t d 20 - 39 tudi chiem X</ le 68,2%, nQ mac benh la chu yeu vdi ty le 9 nuf/1 nam. Lda tudi va gidi tinh mac benh cung phu hpp vdi nhieu nghien cdu khac trong nUdc va ngoai nude ve benh SLE [2].
4.2. Dgc diem mpt so bieu Men lam sang Trong nghien cdu nay chung tdi ghi nhan ngoai cac bleu hien lam sang thudng gap cCia deft tien trien eua SLE nhU: Viem khdp, dau cd, ban da, loet mieng, sdt la cac bleu hien thudng gap (Bang 1) nhu eac nghidn cufu khac [6]. Cac bieu hien cua SLE tien trien nang do tdn thuong than nhu phu chiem ty le 34,8%, tang huyet ap chiem x^ Id 13,4% va cac bleu hien cua ton t h u o n g than kinh trung Udng nhU: Co giat 15,2%, rdi loan tam than 20,5% (Being 1). Nghien
CLfu eua ehung tdi cho thay ty le bieu hien than kinh trung Udng cao hon cac nghien cdu khac [1].
4.3. Dgc diem can Idm sdng 4.3.1. Ddc diem cdc chi so huyet hoc
Ket qua nghien cdu cung cho thay cd 90/112 (80,4%) benh nhan cd bieu hien rdi loan huyet hpe. Tuy theo nghien cufu thi ty le rdi loan huyet hpc cung khac nhau: Nghien cdu cua Hoang Tram Anh la 83,8% [1], nghien cdu cua Al-Shamahy la 64,4% [6]. NhUvay bieu hien rdi loan huyet hpc tuy cd khac nhau tuy nghien CLfu nhUng cung la mot bieu hien rat thudng gap trong SLE, nhat la SLE ed ddt tien trien.
4.3.2. Ddc diem cdc chi sd sinh hod mdu Cac rdi loan sinh hda dang chu y cua nhdm benh nhan nghien cdu la giam protid mau 69,6%, giam albumin mau 92,1% (Bang 3). Cae chi so nay phan anh tinh trang phan ldn benh nhan trong nhdm nghien cufu cd tdn thUdng than hoac cd tinh
JOURNAL OF 108 - CLINICAL MEDICINE AND PHARMACY VoL12-N''8/2017
trang suy kiet cO the do benh nang keo dai. Nghien cdu cua Yip eho thay albumin mau ed vai trd quan trpng trong chan doan SLE dot tien trien va cd lien quan chac che den ehi sd SLEDAI [91. Ket qua nghi&n edu cho thay bieu hien suy than chiem 23,2% {Bang 3), nghien cdu cua Phan Quang Boan d benh nhan viem than lupus ty Id benh nhan bj suy thSn la 31,64% [3]. Nhu vay ty le benh nhan bj suy than d benh nhan SLE khae nhau tuy theo nghien cUu va tuy theo giai doan tien trien cua benh.
4.3.3. Ddc diem ch! so lipid mdu
Rdi loan lipid mau trong nhdm benh nhan nghien cUu cung la mdt bieu hien thudng gap vdi tang cholesterol la 66,7% va tang triglycerid la 87,9%
(Bang 4). Nghien cdu cda Nguyen PhUdng Thuy tinh trang roi loan llpide mau d benh nhan lupus cd hdi chUng than hu cho thay tang cholesterol 89,5%, tang triglycerid 94,7%, tang LDL-cholesterol 55,3%, giam HDL-choleterol 21,1% [5]. Nghien cufu eua Sajjad d benh nhan viem than lupus ed tinh trang tang cholesterol 55,4%, tang trigiycerid 58,5%, tang LDL-cholesterol 30,8%, giam HDL-cholesterol 21,5%
va rdi loan lipid mau cd lien quan vdi tinh trang protein nieu > l g / 2 4 g i d [12], NhUvay tinh trang rdi loan lipid mau d SLE khac nhau tuy nghien cdu va rdi loan lipid mau rat thudng gap.
4.3.4. Ddc diem nudc tieu
Bieu hien tieu dam gap hau nhu cd d tat ca benh nhan nghien cufu ehiem 94,6%, tieu mau 80,4%, tieu bach cau 15,2%, ty le benh nhan ed protein nieu > 0,5g/24 gid la 76,8%, hpi chdng than hu 50% (Bang 5). Nghien cdu cua Pham Cdng Chinh viem cau than la 57,14% va hdi chdng than hU 5,7%
[2], nghien cdu eua Al-shamahy tdn thuong than gap 53% [6], Cd the xae dinh tdn thUdng than trong lupus la rat thudng gap va mdt trong cac yeu t d danh gia tien trien va tien lUdng benh.
4.3.5. Ddc diem tdn thdong cdc coquan Trong nghien cUu nay chung tdi thay ed cac tdn thuong d cac cd quan npi tang nhU: Huyet hpc, than, than kinh, tim mach, hd hap rat thudng gap (Bang 6). Ket qua ty le ton thUdng ndi tang trong ddt tien trien nang lupus eua chung tdi eung cao hdn cac
nghien cdu khae nhU Al-Shamahy [6]. Giai thich cho su khae nhau nay la do nghien edu eua ehung toi ehu yeu tap trung cho eac bdnh nhSn lupus eo dot tien trien nang cdn cac nghien edu khac thl danh gia chung khi cd dot tien trien. NhU vay ty le tdn thuong ndi tang cao la rat thudng gap trong benh SLE co ddt tien tridn nang.
4.3.6. Dgcdiem mgtsd khdng thetumien Cae khang the t u mien trong nhdm benh nhan nghien cdu cho thay ANA dUdng tinh la 98,2%, anti-ds DNA 79,5%, anti-Sm 42,7%, anti-cardiolipin IgM 6,8%, anti-cardiolipin IgG 27,2%, anti-SSA 51%, anti-SSB 13% (Bang 7). Theo nghien cdu Pham Van Thde thi t;^ le ANA (-I-) 66,76%, anti-dsDNA (+) 60,92% [4], nghien edu cua Hoang Tram Anh thi ty le anti-dsDNA {+) 60,5% [1]. Nghien cdu eua Al- Shamahy cho thay ANA {+) 95,3%, anti-dsDNA (+) 59,7%, anti-Sm (-I-) 27,5% [6]. Ty le cac khang the tir mien dUdng tinh cd t h e khac nhau tuy nghien edu, mdt sd khang the ngoai gia tri chan doan con co gia tri tien lUpng benh.
4.3.7. Dgc diem ndng dd cdc bd the, immunoglobulin mien dich
Ket qua nghien cUu (Bang 8) cho thay hau het benh nhan deu cd giam ndng dp C3 (94,6%) va C4 (63,4%) dieu nay phu vdi nhieu nghien cufu vd nong dp C3, C4 trong nghien cdu benh ly SLE d giai doan hoat ddng [6]. Ve cac Ig mien djch trong nghien cilu nay chung tdi nhan thay cd 80% cd tang IgE mien djch (Bang 8). Nghidn edu cda Liphaus va edng sUthi IgE tim t h i y tang d 45% benh nhan lupus va khdng lien quan den tinh trang dj dng hay nhiem ky sinh trung va tac gia nhan dinh IgE can dupe xem nhif mdt bieu hien rdi loan mien djeh d benh nhan SLE [7]. J^ le g i i m ndng dp C3, C4 la rat thudng gap, co mdt ty le Idn benh nhan cd ndng do IgE tang cao d benh nhan lupus cd ddt tien trien nang dUpc ghi n h i n qua nghien cdu nay.
4.3.8. Dgc diem ndng dd cdc cytokine (TNFA, IL6, ILIO) Ket q u i nghien cdu cho thay cd sU tang ndng d d TNFA d nghien cdu nay la 40,4% (Bang 9), gan n h u cac bdnh nhan nghidn cdu deu eho thay c6 tang ndng do 1L6 la 95,7% va tang 111 0 la 85,1 %- Cac
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TAP CHI Y DUpc LAM SANG 108 Tap 12-So 8/2017
cytokine ddng vai trd quan trpng cd ehe benh sinh eua SLE va m d t so nghien cdu cho thay cd sU lien quan giCfa ndng dp cytokine vdi tdn t h u o n g co quan dich. Nghien edu cila Postal [8] cho thay ndng dp TNFA tang eao d SLE hoat ddng so vdi nhdm ehdng.
5. Ket luan
Trong SLE tien trien nang ngoai cac bleu hien rat thudng gap d da - niem mac, khdp, eac bieu hien tdn thuong npi tang nhU: T h i n kinh trung uong, than, huyet hpc, t i m - phdi... cung thudng gap tren lam sang. Ty le xuat hien cac khang the t u midn va rdi loan cac chi sd mien djch eijng rat da dang. Diem dang luu y trong nghien cdu nay eho thay cd mot ty le ldn benh nhan cd tinh trang tang IgE, rdi loan lipid mau va tang cac cytokine TNFA, IL6va ILIO.
Tai li^u tham khao
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2. Pham Cong Chinh (2012) Nghiin cdu ddc diem idm sdng, can Idm sdng binh nhdn lupus ban dd hi thdng dieu tri tgi Khoa Da lieu Binh viin Da khoa Trung UOng Thdi Nguyin. Y hpc Thuc hanh, 11 (851),tr. 36-38.
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Nguyen Phuong Thuy, Dd Thj Lieu, Le Dinh Roanh (2005) So sdnh cdc dgc diem Idm sang, sinh hgc, mo binh hqc cua hgi chdng than hu nguyen phdt vd hdi chdng thdn hu thd phdt d benh nhdn lupus ban do hi thdng dngudi trudng thdnh. Tap chi Nghien cUu Yhpe, 33, t r . l 10-116.
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