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Presentation of
Case
The 66-year-old woman had been well in the past except for
a history of multiple bone pain for which she sought medical
attention at an orthopedic clinic last year; the symptom did
not significantly improve with the prescribed medications. She
complained of one episode of exertional dyspnea after climbing
to two flights of stairs about one year earlier. She didn't
note other symptoms such as chest pain, palpitation, nocturnal
dyspnea and leg edema at that time. Since 9 months before this
admission, exertional dypnea worsened, which persisted about 5
minutes and was relieved after resting. Leg edema and
distended abdomen developed gradually. Progressive exertional
dyspnea, dry cough and orthopnea subsequently developed in
recent 1 month. There was no preceding or associated fever,
sore throat, or chest pain. She visited our emergency service
where chest X ray revealed cardiomegaly. With the impression
of congestive heart failure, diuretics furosemide was
prescribed and she was then admitted for further management.
She did not consume alcohol, or tobacco, and had no recent
history of animal contact or travel.
On examination, she had clear consciousness but was
ill-looking. Her height was 154.6 cm and weight 49 kg. The
temperature was 37.1°C, the pulse rate 90 beats per minute and
the respiratory rate 20 breaths per minute. Blood pressure
while in supine position was 100/60 mmHg. Her conjunctivae
were pink, the sclerae were anicteric and the pupils were
isocoric with prompt light reflexes. The neck was supple
without goiter, lymphadenopathy, or carotid bruits. Engorged
jugular veins to the angle of jaw at 45°were noted. The chest
wall expansion was symmetric and breath sounds were basal
crackles bilaterally. The heart beats were regular without
audible murmur. The abdomen was mildly distended and bowel
sounds were normo- to hypoactive. Hepatomegaly was noted with
an estimated liver span was 14 cm at the right mid-clavicular
line. The extremities were freely movable with grade IV
pitting edema.
Laboratory
data
1. CBC/DC
|
WBC |
RBC |
HB |
HCT |
MCV |
MCHC |
PLT |
|
K/μL |
M/μL |
g/dL |
％ |
fL |
g/dL |
K/μL |
|
9.76 |
4.07 |
12.2 |
37.1 |
91.2 |
31 |
291 |
2. Biochemistry and electrolytes
|
Globulin |
ALB |
T-Bil |
AST |
ALT |
UN |
CRE |
|
g/dL |
g/dL |
mg/dL |
U/L |
U/L |
mg/dL |
mg/dL |
|
9.9 |
2.5 |
0.36 |
22 |
22 |
21.4 |
0.9 |
|
Na |
K |
IgG |
Kappa free
light chain |
Lambda free
light chain |
Beta-2
Microglobulin |
|
mmol/L |
mmol/L |
mg/dl |
Mg/L |
Mg/L |
Mg/L |
|
136 |
3.5 |
5020 |
0.71 |
897 |
12.0 | 3. Urine analysis
|
Appearance |
Sp. Gr |
pH |
Protein |
Glucose |
Ketone |
Bacteria |
|
|
|
|
g/dL |
mg/dL |
|
|
|
Y;C |
1.001 |
7.0 |
- |
- |
- |
- |
|
Urobilirubin |
Bilirubin |
Nitrate |
WBC |
RBC |
Epi |
Cast |
|
|
|
/HPF |
/HPF |
HPF |
|
|
|
0.1 |
- |
- |
0-1 |
- |
0-1 |
- |
Course and
treatment
A chest radiograph revealed
cardiomegaly and bilateral lower lung field infiltration (fig 1
).Electrocardiography
revealed relative low QRS voltage and the QS complexes in
V1-V2 leads mimick anteroseptal wall infarction. Actually it
is a pseudo-infarction pattern (fig 2). Echocardiography
showed bi-atrial enlargement, left ventricular hypertrophy
with sparkling myocardium, (fig 3 and 4
) fair left ventricular systolic function but
restrictive pattern of diastolic dysfunction. Bone survey
revealed numerous small mouth-eaten osteolytic lesions scattered at the
skull, spine, pelvis, and bilateral upper and
lower limbs. Serum immunoflourescent electrophoresis (IFE) revealed a very
dense band of IgG/lambda monoclonal gammopathy. Urine IFE revealed
a thin band of IgG/lambda, plus a very dense band
of lambda chain Bence-Jones protein. Bone marrow study
reported multiple myeloma. Multiple myeloma, IgG/Lambda type, ISS stage
III with amyloid cardiomyopathy was diagnosed. Chemotherapy
was suggested by a consulting hematologist, which the patient
herself did not accept. Instead, she underwent melphalan 4 mg
bid) and prednisolone 10 mg bid) therapy. Dyspnea and leg
edema mildly improved with use of diuretics. She was then
discharged and regularly followed up as an outpatient.
Discussion
澱粉樣變(Amyloidosis)為一種不正常蛋白質-澱粉樣物(amyloid)沉積在身體各處組織及器官的系統性疾病。澱粉樣物的沉積可能只是局部在某一種組織，這種侷限性澱粉樣變對人體健康通常不會有明顯的危害。而系統性的澱粉樣變則會逐漸的取代正常的細胞組織，常見沉積在人體的心臟，嚴重的話對生命健康造成威脅。
系統性澱粉樣變現今依成因用兩個英文字母分為三類:第一個A字母表示amyloid，第二個字母表示沉積於組織的蛋白質。其分別為
- 原發型澱粉樣變 Primary amyloidosis (AL)
- 次要型澱粉樣變 Secondary amyloidosis(AA)
- 遺傳性澱粉樣變Hereditary amyloidosis (ATTR)
原發型澱粉樣變(AL amyloidosis)
發病原因不明，以「多發性骨髓瘤」最常見，造成的原因是因為骨髓中的漿細胞(Plasma
cell)不正常的過度分泌澱粉樣輕鏈(amyloid light
chain)沉積於多個系統組織，包括有心臟，肺部，腸胃道，肝臟，腦部或腎臟，只有不到5%的原發型澱粉樣變(AL
amyloidosis) 只影響心臟一個器官。
次要澱粉樣變 Secondary amyloidosis(AA)
以慢性發炎性疾病為主，屬於AA型澱粉樣，如結核、風濕性關節炎(RA)、骨髓炎、Hodgkin's淋巴瘤、克隆氏症(Crohn's
disease)等。會影響腎、肝、心、脾、淋巴結、血管系統、皮膚等。
ATTR家族澱粉樣變是因為transthyretin的沉積而造成身體病變。在這三類系統性澱粉樣變中，以原發型澱粉樣變
Primary amyloidosis (AL)造成的心肌病變最為嚴重，預後最差。
發生類澱粉沉積的年齡多在40歲以上，男女發生機率均等。臨床表徵呈多樣性，要看所侵犯的器官而定
。而原發性型澱粉樣變心臟病臨床上的症狀可能是輕微無症狀，有三分之一的人有明顯臨床症狀，主要表現為右心衰竭，如雙側肢水腫，肝腫大等等。
原發型澱粉樣變心臟病心電圖的典型表現約為50%的人會有肢導導極振幅偏小，及一些非特異性傳導障礙。典型心臟超音波的表現，主要為心臟任何部位因受類澱粉物質浸潤的結果而增厚且心肌亮度增加(sparkling
myocardium)，如左右心室、心室及心房中隔，甚至僧帽瓣與三尖瓣也都會變厚，由於心肌肥厚，嚴重時心室腔會顯得狹小，心室擴張度不佳，左右心房擴大等窄縮性心肌病變等特徵出現。
原發型澱粉樣變心臟病的確定診斷主要是藉由組織切片。一是藉由心內膜切片確定有澱粉樣物(Amyloid)的沉積。亦或是心臟檢查有特別澱粉樣變變化再加上在其他組織如直腸，腹部脂肪或腎臟有澱粉樣物Amyloid的沉積。而目前對於原發型澱粉樣變心臟病的治療分為兩個部份，一部份主要是以利尿劑來治療心臟衰竭症狀，一部份則是治療導致澱粉樣變心臟病的成因。多發性骨髓瘤造成之
AL澱粉樣變心臟病患者治療主要是用糖皮質激素和免疫抑制劑等來治療多發性骨髓瘤。而自體造血幹細胞移植被認為是治療原發性系統性澱粉樣變性最有效、最有希望的方法。因為原發型澱粉樣變心臟病常伴隨有澱粉樣物沉積於其它組織，所以此種窄縮性心肌症並不適合心臟移植，若臨床上已出現心臟衰竭等症狀，預後不佳，其平均存活率只有6個月。
References
- Falk, RH. Diagnosis and management of the cardiac
amyloidoses. Circulation 2005 Sep
27;112(13):2047-60.
- Hare JM. The Dilated, Restrictive, and Infiltrative
Cardiomyopathies. In: Libby P, Bonow RO, Mann DL, Zipes DP.
Braunwald's Heart Disease: A Textbook of Cardiovascular
Medicine. 8th ed Chapter 64
- Dubrey SW; Cha K; Simms RW; Skinner M; Falk RH.
Electrocardiography and Doppler echocardiography in
secondary (AA) amyloidosis. Am J Cardiol 1996 Feb
1;77(4):313-5.
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Case Discussion
繼續教育考題