|
This 39-year-old male had been
quiet well in the past until five weeks earlier when pain of
the right wrist developed. Initially, he thought the pain was
related to his job and he did not pay attention to it. Due to
progressive painful symptom with limitation of range of
motion, he visited the orthopedic clinic at Far Eastern
Memorial Hospital and oral and topical analgesic agents were
prescribed. Magnetic resonance imaging (MRI) of the right
wrist was arranged due to persistent symptoms. One month
before this admission, he received a diagnosis of HIV
infection with Pneumocystis jirovecii (formerly
P. carinii) pneumonia and oral candidiasis, for which he
was hospitalized at Far Eastern Memorial Hospital and treated
with trimethoprim-sulfamethoxazole (TMP-SMX) and prednisolone
for 12 days. After discharge, he was referred to infection
clinics of this hospital on the same day for antiretroviral
therapy. CD4 count, antibody tests for HIV, HBV and HCV
profiles, and titers of Venereal Disease Research Laboratory
(VDRL) and Treponema pallidum hemagglutination
antibody (TPHA) were determined as baseline evaluation for HIV
infection and AIDS. Ten days before admission, he started to
notice vesicles and a painless ulcer on the glans penis.
Desquamation over the soles and palms developed later.
Subsequently, there were floaters and blurred vision in the
left eye. VDRL titer was 128 and a diagnosis of secondary
syphilis was made. Benzathine penicillin G 2.4 MU was given
once intramuscularly. Rigors, coldness of the four limbs, cold
sweating, and generalized malaise were noted half an hour
later after receipt of penicillin. He became bedridden for one
day and blurred vision of the left visual field worsened, with
development of conjunctival congestion, ocular pain and
epiphora. Then he was admitted for his rapid progression of
blurred vision. He has been a bisexual and had unprotected sex
with an HIV-infected male six months earlier.
On physical examination, he was alert and oriented.
The body temperature was 36.2°C, blood pressure was 126/85 mmHg,
the heart rates were 98 beats per minute and the respirations
were 20 breaths per minute. Oxygen saturation was 98%
while he was breathing ambient air. The pupils were
equal and reacting to light; full range of eye movement was
not limited. Left conjunctiva was injected and sclera
was anicteric. Cloudiness was noted in the anterior chamber
of the left eye. The neck was supple with
no lymphadenopathy or jugular venous engorgement. The heart beats were
regular without audible murmur. Clear breath sounds were heard on chest
auscultation. The bowel sound was normoactive; the abdomen
was soft; no shifting dullness or tenderness was noted.
Liver span was about 8 cm over the right mid-clavicular
line. Spleen was impalpable. The extremities were freely movable with no
edema. Right wrist tenderness was noted without limitation of
range of motion. Vesicles and ulcer over his
penis and desquamation at the palms and soles
were noted.
Hemogram showed no leukocytosis
(WBC 7440/ul), with 81.5 % neutrophils, and normocytic anemia.
The results of serum creatinine, sodium and potassium were
normal except abnormal liver function.
< Laboratory Values
>
Hemogram
| Date |
WBC
K/μL |
HB
g/dL |
PLT
K/μL |
Lym
% |
Mon
% |
Eos
% |
Bas
% |
Neu
% |
CRP
mg/L |
| 11/24 |
7.44 |
9.6 |
442 |
7.5 |
8.3 |
2.6 |
0.1 |
81.5 |
|
| 12/15 |
3.91 |
12.4 |
365 |
37.1 |
13.8 |
4.6 |
0.5 |
47 |
0.24 |
| 12/23 |
4.52 |
12.1 |
352 |
41.4 |
11.5 |
4.9 |
0.4 |
41.8 |
|
| 3/3 |
3.58 |
13.8 |
275 |
37.4 |
8.4 |
14.2 |
0.3 |
39.7 |
|
Biochemistry
| Date |
BUN
mg/dL |
Cre
mg/dL |
Alb
g/dL |
AST
U/L |
ALT
U/L |
T-Bil
mg/dL |
D-Bil
mg/dL |
ALP
U/L |
Na
mEq/L |
K
mEq/L |
LDH
U/L |
TP
g/dL |
| 2008/11/24 |
|
0.9 |
|
|
193 |
|
|
|
135 |
4.1 |
|
|
| 2008/12/3 |
|
|
3.6 |
24 |
|
|
|
|
136 |
4.1 |
454 |
6.6 |
| 2008/12/15 |
13 |
0.9 |
4.53 |
52 |
26 |
0.29 |
|
147 |
|
|
|
|
| 2008/12/23 |
17.7 |
1.0 |
|
59 |
15 |
1.01 |
0.31 |
141 |
|
|
544 |
|
| 2009/3/3 |
|
1.1 |
|
|
15 |
|
|
|
|
|
|
|
S.T.S profiles
| |
VDRL/RPR
test |
TPHA
test |
VDRL |
TPHA |
| |
Blood |
Vitreous fluid |
| 2008/11/24 |
1:128 |
>1:20480 |
|
|
| 2008/12/4 |
|
|
1:4~8 |
1:1280 |
| 2009/3/3 |
1:64 |
1:10240
|
|
|
Lipid profiles and
glucose
| |
T-CHO
mg/dL |
TG
mg/dL |
LDL
mg/dL |
HDL
mg/dL |
GLU-AC
mg/dL |
| 2008/11/24 |
274 |
58 |
|
|
|
| 2008/12/23 |
211 |
142 |
104 |
78.6 |
|
| 2009/3/3 |
230 |
75 |
|
|
79 |
HIV profiles
| |
HIV viral load
(RNA copies/ml) |
CD4 count
(cells/μL) |
| 11/17 |
|
92 |
| 11/24 |
76700 |
106 |
| 12/23 |
747 |
243 |
| 3/3 |
undetectable |
227 |
CSF profiles
| Appearance |
India ink
smear |
TP
g/dL |
Glucose
mg/dL |
LDH
U/L |
Cell count
cells/μL |
L/N |
TPHA
titer |
Cryptococcus
Antigen |
| Clear |
negative |
89.5 |
40 |
53.9 |
18 |
18/0 |
1:128+ |
<
1:2 |
Culture results
| |
Bacteria |
Fungi |
Mycobacterial culture |
| Blood |
No growth |
No growth |
|
| CSF |
No growth |
No growth |
|
| Aqueous |
No growth |
No growth |
|
| Vitreous aspirate |
No growth |
No growth |
|
| Right wrist aspirate |
No growth |
No growth |
No growth
|
< EKG >
Left axis deviation
< Image Study >
Chest radiography:
bilateral perihilar hazziness
MRI of the right wrist:
granulomatous inflammation of the distal radio-ulnar joint and
osteonecrosis of the right lunate bone
< Course and Treatment
>
After admission, combination antiretroviral therapy, Kivexa
(abacavir plus lamivudine) and atazanavir, was commenced.
Aspiration of the aqueous humor and vitreous fluid was
performed after consulting with an ophthalmologist.
Intravitreal administration of vancomycin and ceftazidime were
given empirically. Analysis of a CSF specimen yielded
pleocytosis with lymphocyte predominance, mildly elevated
protein level and a TPHA titer of 1:128. Aqueous penicillin
was started at a dose of 3 million units, every four hours.
His visual acuity became improved as well as the lesions of
the skin and external genitalia. Cultures of specimens of
blood, CSF, aqueous humor and vitreous fluid were all
negative. Study of vitreous fluid specimen revealed a VDRL
titer of 4-8 and a TPHA titer of 1280. MRI study of the right
wrist suggested granulomatous inflammation of the distal
radio-ulnar joint and osteonecrosis of the right lunate bone.
CT-guided aspiration was done. Cultures for fungi, bacteria
and mycobacteria yielded no growth. Right wrist pain resolved
after penicillin therapy. He was discharged after a 14-day
course of penicillin therapy and was followed regularly at our
ID clinics.
< 病例分析
>
梅毒是由梅毒螺旋體(spirochete)的病菌所引致之一種臨床症狀複雜、變異性大的慢性性傳染病。因此有著”大冒充者
”(“the great imitator”)的別名。現代醫學之父Sir William Osler更是讚揚為“He who
knows syphilis, knows
medicine”。螺旋菌入侵人體通常在皮膚或黏膜破損處，在該處形成頗具特徵性之原發性病灶。感染後不久，螺旋菌很快散播全身，可以侵犯幾乎全身之器官及組織，產生變化多端之臨床症狀。梅毒主要由性交傳染，也可經由輸血感染；或婦女懷孕時罹患梅毒，經由胎盤而感染胎兒，造成先天性梅毒。梅毒乃第三類傳染病，衛生署規定發現梅毒需一週內通報。
根據傳染期程及傳染性之有無，梅毒分為早期(early
syphilis)及晚期梅毒(late
syphilis)。早期梅毒指感染後兩年內之時期，包括初期梅毒、二期梅毒、復發性梅毒以及早期隱性梅毒(early
latent
syphilis)。早期梅毒傳染性較強；罹患梅毒超過一年以上，通常傳染性較弱，是為晚期梅毒，包括︰晚期隱性梅毒(late
latent syphilis)和三期梅毒(tertiary
syphilis)；其中包括︰晚期隱性梅毒，以及心臟血管性及神經性梅毒。
初期梅毒在感染後3~90天(平均三週)在接觸處出現無痛性潰瘍。多為單個病灶，潰瘍界限分明，表面呈肉紅色糜爛，不易出血，邊界及底部有浸潤化而呈硬感，觸摸之如感覺皮下埋一鈕扣狀，故有硬性下疳(chancre)之稱，無壓痛感，但壓之有清澈之滲出液溢出，內含大量之梅毒螺旋菌，故傳染性極高。局部淋巴腺腫大隨硬性下疳出現不久即發生，淋巴腺腫不痛，無壓痛感，堅實似橡皮，各自單獨存在不相結合，不與皮膚或皮下組織沾連。硬性下疳好發於男性陰莖上任何部位，女性則好發於陰部，亦可能出現於身體任何部位。
縱使沒有治療，硬性下疳在出現後四至十週會逐漸消失，而梅毒螺旋菌已從淋巴結進入血液並散播全身，以致全身組織器官全受影響，包括皮膚、中樞神經系統、關節、肝臟等。皮疹是二期梅毒最常見之症狀，常為全身對稱性，多無自覺症狀，可出現於手掌及足蹠，此為梅毒感染之一大特性。皮疹之形態包括斑疹、丘疹、脫屑性丘疹及膿。在身體皺褶處（如肛門）之皮疹，由於濕熱及磨擦產生表淺性潰瘍，稱「扁平濕疣
(condyloma
latum)」，內含無數梅毒螺旋菌，故具高傳染性。二期梅毒之皮疹與多種其他皮膚疾病外觀類似，容易導致誤診，不可不慎。全身性淋巴腺腫也是二期梅毒常見症狀之一。腫大之淋巴腺堅實似橡皮，各自分立不相融合，無壓痛，好發於鼠蹊、頸部、枕部、腋部及上髁部之淋巴腫。
梅毒在早期(初期或二期)時中樞神經系統常被侵犯，但大部分病人沒有症狀，稱為無症狀性早期神經梅毒；另有百分之五的病人會出現症狀，包括腦膜炎、腦神經炎等。根據過去文獻指出，眼睛的侵犯不局限於任何梅毒時期；眼睛的任一解剖構造都有可能被侵犯。早期神經性梅毒通常侵犯腦膜及血管，故稱為腦膜血管性梅毒
(meningovascular syphilis)。
二期梅毒症狀經過數週到一年長短不定之時期會自動消失，而進入完全無臨床症狀的時期，可分為早期隱性梅毒及晚期隱性梅毒。早期隱性梅毒為感染後未超過一年之無症狀期，病患仍具傳染性；晚期隱性梅毒則指感染超過一年之無症狀期，傳染力較弱。隱性梅毒之診斷端賴過去病史，以及陽性梅毒血清反應。在這段時期內，復發性皮疹及黏膜病灶可能再度出現，造成復發性梅毒。
三期梅毒屬晚期梅毒，主要有三種表現，梅毒腫(gumma)、心臟血管性梅毒及晚期神經性梅毒。平均而言感染後15至20年才出現。梅毒腫，好犯皮膚、上表皮組織以及骨骼肌肉組織。心臟血管性梅毒，病變主要是主動脈炎、冠狀動脈入口狹窄、動脈瘤等。晚期神經性梅毒，主要侵犯腦實質(brain
parenchyma)及脊髓後柱(posterior column)。
當人體受到梅毒螺旋體的感染之後，體內的免疫反應會導致許多抗體的產生，這些抗體基本上可分兩種類型：對抗梅毒螺旋體的特定性抗體（specific
anti-treponemal
antibody）及梅毒螺旋體侵犯體內組織而產生的非特定性抗體，又稱反應素（non-specific reaginic
antibody）。前者之檢驗法，包括︰螢光螺旋體抗體吸附試驗法FTA-ABS（fluorescent treponemal
antibody- absorption）具敏感性及高專一性，但方法較複雜；另有梅毒螺旋體血球凝聚試驗 TPHA（T.
pallidum hemagglutination
assay）靈敏度高，而方法也較為簡單；後者使用含有脂質抗原（lipoidal
antigen），最常用者為VDRL及RPR（rapid plasma
reagin）。愛滋感染病患若受到梅毒感染，常會出現不典型的症狀。初期梅毒會出現多個潰瘍，潰瘍會更大更深，癒合所需時間會更久。初期梅毒症狀尚未消失前，有百分之七十五之病患二期梅毒即表現。
一期、二期或早期隱性梅毒病患，適用長效盤尼西林(benzathine
penicillin)，使用劑量為2.4 million unit
(MU)，1次肌肉注射完成治療；對不能每天接受注射，以及合作程度不好的病人最適宜。對於晚期隱性梅毒、感染期間不明病患或三期梅毒病患，一週一次，需注射三週治療。對於神經性梅毒，必須使用aqueous
crystalline penicillin靜脈注射10至14天，劑量為每天18-24
MU、分六次給予。一期、二期或早期隱性梅毒、同時感染愛滋病毒者，其治療劑量專家建議可能需要比照晚期梅毒。
對penicillin產生過敏者，應考慮作desensitization。對過敏史有懷疑者，應考慮作盤尼西林皮膚試驗確診之。自penicillin發明以來，梅毒螺旋體並沒有對penicillin產生抗藥性。Penicillin仍然是治療梅毒的首選藥物。在美國疾病管制局的指引中指出doxycycline，ceftriaxone，tetracycline可當作替代藥物，但需要大規模的研究去進一步評估這些藥物的有效性。當患者為神經性梅毒、先天性梅毒、孕婦或同時感染愛滋病毒者，更應考慮penicillin為第一線用藥。目前並沒有臨床研究證明其他藥物對以上患者有效。
使用penicillin來治療梅毒時，不論梅毒分期，有百分之十的病患會產生Jarisch-Herxheimer
reaction。若為二期梅毒患者，其發生率可高達70-90%。通常病患在注射penicillin後1至2小時即出現急性發熱反應，其症狀包括；發燒、頭痛、肌肉酸痛、全身無力等，以上症狀在二十四小時內自行恢復。其發生機制為大量梅毒菌死亡後誘發體內免疫系統產生之細胞激素(cytokines)釋放有關。過去有案例報告，當梅毒菌侵犯眼內時使用penicillin，會引發局部發炎反應，嚴重影響視力。因此有專家建議，施打penicillin前使用類固醇以減少嚴重後遺症發生。
以下梅毒病患，應考慮作腦脊髓液檢查，包括有神經學症狀、眼睛症狀、耳朵症狀、同時感染愛滋病病毒並CD4數目小於350
cells/μL或血清RPR titer大於1:32者，治療失敗，懷疑三期梅毒或病程不確定時。
< References >
Mandell: Principles and Practices of infectious diseases,
6th ed.,2005
Golden MR, et al. JAMA 2003;290:1510-1514.
Rompalo AM, et al. Sex Trans Dis 2001;28:448-54
Schofer H, et al. Genitourin Med 1996;72:176-81
Laura
A. Teasley, et al. Int Ophthalmol Clin 2007;47:133-44.
Fathilah J, Choo MM. Med J Malaysia 2003;
58:437-439.
| 
Case Discussion
繼續教育考題