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系統性紅斑狼瘡併抗磷酯症候群
(antiphospholipid
syndrome, Hughes syndrome)
<Case
presentation>
Chief complaint
A 34 year-old female
was admitted to the infectious disease ward because of fever,
swelling of bilateral lower legs and a wound on the lateral
malleolus of her left foot for more than one week
Past history
- Drug allergy(-), Food allergy(-)
- Smoke(-), Alcohol(-)
- Hypertension(-),DM(-)
- Surgical intervention(-)
- Occupation: nil
- Education: 高職農工
Clinical
course:
- 1994-April: She was admitted to our
neurology ward due to incoherent, irrelevant speech and mild
fever for 2~3 weeks. Cerebrospinal fluid (CSF) study and
immunological data showed normal results. Major depression
was suspected
- 1994-May: She was admitted to our
ophthalmology ward due to blurred vision. Optic neuritis R/O
multiple sclerosis was suspected. But MRI showed ischemic
change at left thalamus and bilateral hypothalamus.
Vasculitis such as systemic lupus erythematous (SLE) was
suspected.
- 2003-April: She was admitted to
our neurology ward due to intermittent numbness around the
trunk associated with an unstable gait and urinary
incontinence for 6 months. Agarose gel electrophoresis of CSF
showed oligoclonal bands. The evoked potential response
test was abnormal. MRI revealed multiple spinal cord lesions that
were consistent with multiple sclerosis involving the spinal
cord below C1 level. Multiple sclerosis was diagnosed. She
received one course of interferon treatment. The sequelae
were paraplegia and nearly total blindness. She lost to
follow-up for more than 2 years and received herb drug
treatment intermittently.
- 2005-September: She got a wound on the lateral malleolus
of left foot accidentally, then fever and swelling of
bilateral lower legs developed. She was admitted to a local
hospital due to suspected cellulitis. However after
receiving antibiotics for three days, the fever persisted
and the lower leg edema aggravated. Hence she was referred
to our infectious disease department for further
treatment.
Physical
examination
Consciousness: clear,
E4V5M6
Vital sign: BT:37.8, BP:112/70mmHg, RR: 18/min
PR:76/min
Conjunctiva: not pale sclera: not icteric
Neck: supple, LAP(-) , JVE(-), goiter(-)
Chest: symmetric
expansion,
BS: decrease over bilateral
lungs
HS: regular heart rate, Gr II/VI
Systolic murmur over LLSB
Abdomen: soft &
obese
L/S: impalpable
Shifting dullness(-)
No tenderness, no rebound
pain
Extremities: paraplegia(+) but only light touch
sensation(+), pain sensation(-)
pitting edema
of bilateral lower legs and feet(+)
a wound on
the lateral malleolus of left foot: erythema(+), local heat
(+), yellow
discharge with foul
odor(+)
Palpable inguinal LAPs(-)
Laboratory
data
- WBC: 2830 Hb:11.1 MCV: 92.3
Platelet:140000 ESR: 96mm/1h ��
- Urine protein(-) OB(-) sugar(-) RBC:
0-2/HPF, WBC: 2-5/HPF, Epi: 5-10/HPF ��
- Stool OB(-) ��
- TP: 6.5, albumin: 2.5, GOT:31,
GPT:15, LDH: 149, BUN: 20, Cr:1.47, Na: 138, K: 4.8, CL:
107, AC sugar: 87, Cholesterol: 134, TG: 224, UA: 10.02 ��
- CRP: 17.5 D-dimer: <324 mg/dl ��
- S-iron: 47 mg/dl, UIBC: 143 mg/dl,
Ferritin: 393.5 mg/dl
- Immunological data: as the following table
|
|
1994-03 |
2003-04 |
2005-09 |
|
ANA |
- |
- |
>1:2560 |
|
Anti-DS-DNA |
- |
- |
>400 |
|
RA factor |
14.1 |
139 |
167 |
|
VDRL |
- |
- |
- |
|
LE cell |
- |
- |
|
|
C3 |
|
94 |
22.8 |
|
C4 |
|
11.6 |
5.67 |
|
IgG |
1510 |
|
3370 |
|
IgA |
|
|
328 |
|
IgM |
|
|
101 |
|
PT |
|
11.5/12.3 |
11.1/11.1 |
|
INR |
|
0.88 |
0.94 |
|
PTT |
|
31.6/27.1 |
30.2/29.1 |
|
aCL IgG |
|
|
+ (79) |
|
LAC |
|
|
<1.2 |
|
Anti-Ro |
|
|
(+) (>240) |
|
Anti-La |
|
|
(-) |
|
Anti-Sm |
|
|
(+) (>120) |
|
Anti-RNP |
|
|
(+)(>240) |
|
Anti-Jo-1 |
|
|
(-) |
|
Anti-Scl-70 |
|
|
(-) |
Chest PA:
cardiomegaly R/O pericardial
effusion,
R/O pleural effusion
Cardiac echo
- Moderate pericardial effusion ��
- Moderate TR ��
- Pulmonary hypertension
Classification criteria of SLE
that this patient met:
- ANA(+)
- Oral ulcer(-)
- Malar rash(-)
- Discoid rash(-)
- Photosensitivity(-)
- Serositis(+)
- Renal disorder (-): urine protein(1+)
- Neurological disorder(+)
- Hematological disorder: WBC 2830
- Immunological disorder:
anti-DS-DNA(+) anti-Sm(+), anti-phospholipid Ab(+)
- Arthritis(+)
Final
diagnosis:
- Systemic lupus erythematosus with CNS
involvement
- Antiphospholipid syndrome
<
Analysis>
多發性硬化症，被認為是一種侵犯神經系統的自體免疫疾病。其特徵是發炎、去髓鞘化
(demyelination)、及gliosis。病人的症狀可能緩解、復發或者持續的惡化。
多發性硬化症和大多數自體免疫疾病一樣，女性居多，男女比約一比二，好發年齡約20~40歲。病人的血中可能存在一些對抗髓鞘抗原的自體抗體，例如anti-MOG抗體(myelin
oligodendrocyte glycoprotein)。臨床症狀的出現可能是abrupt或insidious。
多發性硬化症的臨床症狀包括肌肉無力、運動之後肌肉更無力、甚至伴隨著pyramidal
signs例如spasticity、hyperreflexia 及Babinski's
sign。此外還有ataxia、視神經炎、視力減退、複視、感覺神經異常或喪失、眩暈、膀胱及大腸功能失常導致無法解尿、尿失禁或便秘等等。
表一：Initial symptoms of MS
|
Symptom |
Percent of cases |
Symptom |
Percent of cases |
|
Sensory loss |
37 |
Lhermitte |
3 |
|
Optic neuritis |
36 |
Pain |
3 |
|
Weakness |
35 |
Dementia |
2 |
|
Paresthesias |
24 |
Visual loss |
2 |
|
Diplopia |
15 |
Facial palsy |
1 |
|
Ataxia |
11 |
Impotence |
1 |
|
Vertigo |
6 |
Myokymia |
1 |
|
Paroxysmal attacks |
4 |
Epilepsy |
1 |
|
Bladder |
4 |
Falling |
1 | Source:
Harrison's principles of internal medicine 16th ed. P2462.
表二則是多發性硬化症的診斷標準，目前MRI已是診斷多發性硬化症必備的檢查工具。
表二：Diagnostic criteria for MS
- Examination must reveal objective
abnormalities of the CNS.
- Involvement must reflect predominantly disease of white
matter long tracts, usually including
(a) pyramidal pathways,
(b) cerebellar pathways,
(c) medial longitudinal fasciculus,
(d) optic nerve, and
(e) posterior columns.
- Examination or history must implicate involvement of two or more areas of the CNS.
- MRI may be used to document a
second lesion when only one site of abnormality has been
demonstrable on examination. A confirmatory MRI must have
either four lesions involving the white matter or three
lesions if one is periventricular in location. Acceptable
lesions must be >3 mm in diameter. For patients older
than 50 years, two of the following criteria must also be
met: (a) lesion size>5mm, (b) lesions adjacent to the
bodies of the lateral ventricles, and (c) lesions present
in the posterior fossa.
- Evoked response testing may be
used to document a second lesion not evident on clinical
examination.
- The clinical pattern must consist of
(a) two or more separate episodes of worsening involving
different sites of the CNS, each lasting at least 24 h and
occurring at least one month apart, or (b) gradual or
stepwise progression over at least 6 months if accompanied
by increased IgG synthesis or two or more oligoclonal bands.
MRI may be used to document dissemination in time if a new
T2 lesion or a Gd-enhancing lesion is seen or more months
after a clinically isolated syndrome.
- The patient's neurologic condition
could not better be attributed to another disease.
Diagnostic
categories
-
Definite MS: All five criteria
fulfilled.
-
Probable MS: All five criteria
fulfilled except (a) only one objective abnormality despite
two symptomatic episodes or (b) only one symptomatic
episodes despite two or more objective
abnormalities.
-
At risk for MS: Criteria 1, 2, 3,
and, 5 fulfilled; patient has only one symptomatic episode
and one objective abnormality.
抗磷酯症候群(antiphospholipid syndrome,
Hughes syndrome)於1983首先由英國G.R.V.
Hughes教授所描述，歷經多年研究及國際會議討論，於1999年提出抗磷酯症候群的preliminary
classification criteria，如附表：(Arthritis
Rheum 42: 1309, 1999)
抗磷酯症候群因是否伴隨其他自體免疫疾病之有無而分為原發性及次發性，次發性抗磷酯症候群經常伴隨著系統性紅斑狼瘡。其臨床特徵主要是靜脈或動脈血栓或流產及血中有存在抗磷酯抗體。臨床症狀依血栓發生部位而有不同症狀，例如腦中風、肺栓塞、腸子壞死、急性腎衰竭、急性心肌梗塞等等，除此之外有些病人還會出現網狀青斑(livedo
reticularis)、自體免疫溶血性貧血、舞蹈症、肺動脈高壓、心臟瓣膜病變引起心衰竭等，實驗室檢查除了抗磷酯抗體外，有時可看到血小板低下、抗核抗體陽性、抗去氧核糖核甘酸抗體陽性、蛋白尿、VDRL陽性等。本病例抗磷酯抗體IgG高達79
GPL/ml，因此病患可能合併有次發性抗磷酯症候群。不過依據歐洲1000位抗磷酯症候群病人的統計資料，抗磷酯症候群較少發生myelopathy
(0.4%)及視神經病變 (0.1%)。
系統性紅斑狼瘡併中樞神經系統侵犯，主要分為神經(neurological)及精神
(psychiatric)兩方面，臨床症狀包括癲癇、頭痛、腦中風、腦出血、胡言亂語等等，此外有時會引起tranverse
myelitis，造成paraplegia，甚至呼吸衰竭。
本例剛開始因視神經炎被懷疑是多發性硬化症，事實上很多自體免疫疾病例如系統性紅斑狼瘡、修格連症候群等都可能引起視神經炎。因此必須從實驗室檢查的結果及長期追蹤病程才能確定病人的診斷。
多發性硬化症、抗磷酯症候群及系統性紅斑狼瘡併中樞神經系統侵犯等三種病，其臨床症狀非常相似，很難鑑別診斷。G.R.V.
Hughes教授等學者於2005年於Rheumatology這本雜誌發表了一篇文章，探討三者之間的差異，其結論如附表：(Rheumatology
44:434-442, 2005)
MS: multiple sclerosis
PAPS:
primary antiphospholipid syndrome
NPLE/APS:
neuropsychiatric lupus
with/without APS
Reference:
-
Harrison's Principles of Internal
Medicine,
16th ed.
-
Ferreia S, D'Cruz DP, Hughes GRV:
Multiple sclerosis, neuropsychiatric lupus and
antiphospholipid syndrome: when do we stand? Rheumatology
2005; 44:434-442
-
Kelly's Textbook of Rheumatology,
7th ed.
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Case Discussion
繼續教育考題