# 103年內專(200題)101-149

## Question 101:

有一位21歲男性因喉痛，每天發燒，前額頭痛，全身肌肉和關節痛6天而求診。他於發病前一週放完暑假由高雄回到台北。身體診察體溫38.7°C，血壓 102/70 mmHg，脈搏 100/min，呼吸 16/min，後咽有充血現象，但無分泌物，胸部、手臂和下肢有 maculopapular rash，而手掌和腳掌則無皮疹，下背有酸痛，其他心肺和腹部檢查則無異常。實驗血液檢查發現白血球3000/uL (3.0x10 9/L)，血小板86000/uL (86.0x10 9/L)，血紅素13.8 g/dL，ALT 116 units/L，total billirubin 1.2 mg/dL。 請問最可能的診斷為何?

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- A. Leptospirosis
- B. Syphilis
- C. Dengue fever
- D. 水痘
- E. Melioidosis

### Correct Answer: C

**2009 New Dengue Case Definitions**
Dengue without Warning Signs
Fever and two of the following:
Nausea, vomiting
Rash
Aches and pains
Leukopenia
Positive tourniquet test

**Dengue with Warning Signs**
Dengue as defined above with any of the following:
Abdominal pain or tenderness
Persistent vomiting
Clinical fluid accumulation (ascites, pleural effusion)
Mucosal bleeding
Lethargy, restlessness
Liver enlargement >2 cm
Laboratory: increase in HCT concurrent with rapid decrease in platelet count

**Severe Dengue**
Dengue with at least one of the following criteria:
* Severe Plasma Leakage leading to:
– Shock (DSS)
– Fluid accumulation with respiratory distress
* Severe Bleeding as evaluated by clinician
* Severe organ involvement
– Liver: AST or ALT ≥ 1000
– CNS: impaired consciousness
– Failure of heart and other organs

Ref: 美國疾管局(CDC)
http://www.cdc.gov/dengue/symptoms/

## Question 102:

有一位 81 歲女性因發燒、畏寒及嘔吐一天而被送到急診室。身體診察體溫 39℃，血壓 120/72mmHg，脈搏 110/min，呼吸 16/min，心肺及腹部檢查呈現下腹部輕微壓痛。實驗室檢查血液白血球 18000/uL(18.0x10 9/L)，neutrophil 88%；尿液檢查：WBC 100/HPF 且 leukocyte esterase (+)，革蘭氏陰性桿菌；胸部 X 光正常。病人住院接受積極輸液及經驗性 piperacillin-tazobactam 靜脈注射治療。入院後三天，血液及尿液培養出 Klebsiella pneumoniae，其抗生素感受性試驗呈現對piperacillin-tazobactam, imipenem, ciprofloxacin, cefazolin 和trimethoprim/sulfamethoxazole 敏感。 此時抗生素治療最恰當的選擇是什麼？

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- A. 持續給予 piperacillin-tazobactam
- B. 停用 piperacillin-tazobactam 而改用 cefazolin
- C. 停用 piperacillin-tazobactam 而改用 ciprofloxacin
- D. 停用 piperacillin-tazobactam 而改用 imipenem-
- E. 停用 piperacillin-tazobactam 而改用 trimethoprim/sulfamethoxazole

### Correct Answer: B

藥敏試驗顯現 cefazolin(第一代 cephalosporin)即可有效治療 Klebsiella pneumoniae，故可進行降階(de-escalation)。

Ref: 熱病 2015

## Question 103:

一位 22 歲男性，於 4 天前開始解尿有灼熱感，就診前兩天左眼有黃色液體流出，身體診察除發現左眼眼皮有紅腫、左眼有黃色分泌物流出外，生殖器亦可見黃色液體 (如圖)，請問致病原最可能是什麼?


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- A. 肺炎克雷白氏桿菌 (Klebsiella pneumoniae)
- B. 大腸桿菌 (Escherichia coli)
- C. A 族鏈球菌 (group A streptococcus )
- D. 淋病雙球菌 (Neisseria gonorrhoeae)
- E. 金黃色葡萄球菌 (Staphylococcus aureus)

### Correct Answer: D

選項中的細菌只有淋病雙球菌 (Neisseria gonorrhoeae)有如圖的黃色分泌物表現。

Ref: 台灣疾病管制局 淋病治療指引
http://www.cdc.gov.tw/professional/downloadfile.aspx?fid=488F1512AAF6B680

## Question 104:

一名 45 歲的男性，至急診室就醫，有低度發燒，全身倦怠和關節痛。就診 6 週之前曾與男性性工作者發生不安全的性行為。身體檢查發現有多發性丘疹 (maculopapular rash)，涵蓋他的整個身體，包括手掌 (如圖)和腳掌。請問病患的診斷最可能由下列的何種測試得到：


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- A. HIV Western blot antibody test
- B. Tzanck smear
- C. Gram stain
- D. Fluorescent treponemal antibody absorption test
- E. India ink stain

### Correct Answer: D

dangerous sexual history, low grade fever, general weakness, painful joint, general macular popular rash, 此病患處於梅毒第二階段，故以 D. Fluorescent treponemal antibody absorption test 證實梅毒感染

Ref: 台灣疾管局 梅毒治療指引
http://www.cdc.gov.tw/professional/downloadfile.aspx?fid=F7AEFF680C74CF57

## Question 105:

一位 65 歲男性有糖尿病病史，因為高燒和寒顫被送至急診室，右側鼠蹊部位出現紅腫約四天。身體檢查發現：體溫 39.4℃，血壓 100/60mmHg，脈搏 108/min。於右側鼠蹊部位延伸至右側大腿有 12x9 公分的發紅，變硬，腫脹疼痛的病灶。在該病灶上緣還有兩個出血性的水泡(如圖)。骨盆腔的電腦斷層顯示：大腿處軟組織的壞死及少量氣體產生。請問下列何者是此病患最急迫的治療?


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- A. Surgical exploration and debridement
- B. Anti-staphylococcal antibiotics
- C. Anti-pseudomonal antibiotics
- D. Hyperbaric oxygen therapy
- E. Blood transfusion

### Correct Answer: A

DM(+), gangrenous change, erythematous change, blister(+)，高度懷疑 necrotizing fascitis，應緊急 surgical debridement，否則有可能會急速產生 acute septic shock 及 compartement syndrome。

Ref: 美國疾管局 necrotizing fasciitis http://www.cdc.gov/features/necrotizingfasciitis/

## Question 106:

2014 年西非伊波拉病毒感染 (Ebola virus disease)通報超過 1700 例，死亡逾 900例，逾 50 位醫療人員感染，下列相關㔀述何者正確? (應選出所有正確答案)
(1) 此疾病在我國列為第五類法定傳染病，通報時效為 24 小時內完成
(2) 致病病毒之天然宿主主要是駱駝和鼠類
(3) 此病毒可經由受感染動物直接傳給人，而人傳人主因是直接接觸到被感染者或其屍體之血液、分泌物、器官，或間接接觸被汙染之環境而感染
(4) 疾病潛伏期 2 至 21 天，當病人三週內有相關旅遊或接觸史，一旦有發燒、頭痛、肌肉痛、噁心、嘔吐、腹瀉、腹痛，或不明原因出血、死亡等任一項時，即應通報且採檢送驗
(5) 收治病人於負壓隔離病房，醫護人員戴 N95 口罩最為重要

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- A. (1)+(2)+(3)
- B. (2)+(3)+(4)
- C. (1)+(3)+(4)
- D. (1)+(4)+(5)
- E. (1)+(5)

### Correct Answer: C

(2)在非洲，果蝠(尤其是錘頭果蝠（Hypsignathus monstrosus）、富氏前肩頭果蝠（Epomops franqueti）與小項圈果蝠（Myonycteris torquata）)被認為是可能的天然宿主；且伊波拉病毒的地理分布範圍與果蝠的分布範圍重疊。在非洲曾被報告的其他感染動物包括黑猩猩、大猩猩、猴、森林羚羊與豪豬等。

(5) 所有進入安置疑似或確定病例隔離病室的工作人員，則應穿著**連身型防護衣並配戴 N95 等級以上口罩、防護面罩、雙層手套、防水長筒鞋套等高規格個人防護裝備**，若病人有嘔吐或腹瀉症狀時，則加穿防水圍裙，避免直接接觸病患之血液及體液。且優先將病人收置於負壓隔離病室等，提升
醫療照護工作人員防護層級。

Ref: 台灣疾管局：伊波拉病毒防治手冊
http://www.cdc.gov.tw/professional/info.aspx?treeid=BEAC9C103DF952C4&nowtreeid=25125929050639E7&tid=733011E5C5108563

## Question 107:

下列有關病人腹瀉危險因素/症狀及病因之組合，正確為何者?
(應選出所有正確答案)

(1) 血便--- Shigella, Salmonella, E. coli O157
(2) 小孩養烏龜、蜥蜴--- Salmonella
(3) 吃生蛋---Salmonella
(4) 搭郵輪旅遊--- Norovirus
(5) 家中小貓小狗腹瀉--- Campylobacter

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- A. (1)+(2)+(3)
- B. (2)+(3)+(4)
- C. (3)+(4)+(5)
- D. (1)+(2)+(3)+(4)
- E. (1)+(2)+(3)+(4)+(5)

### Correct Answer: E

**Salmonella**
1. 沙門氏菌感染症屬全球分布，在已開發國家（除非有很好的通報系統）大部分的臨床病例沒有被通報，通報率低於 1%，病例最常發生於嬰兒和五歲以下小孩。大約 60%~80%的病例屬於散發病例，其他病例為爆發流行，小的流行通常發生於一般人群，大的流行則常見於兒童醫院或機構、餐廳及護理之家等人口密集機構，大部分的發生原因是食物來源遭受污染，少數是因帶菌者污染食物，或人與人直接糞口接觸引致。本病較易發生在 7 月~10 月，氣候溫暖的季節，目前在世界許多國家的發生率有增加的趨勢。
2. 傳染窩: 動物及人類，動物例如：家禽、豬、羊、馬、牛、齧齒動物及寵物（鬣蜥蜴、烏龜、小雞、蛇、狗、貓…）等。人類慢性帶菌者較少，但在動物及鳥類較為普遍。
3. 傳染方式: 食入被動物或人類糞便污染的水或食物，受污染的食物例如：生的或未煮熟的雞蛋/雞蛋製品、牛奶/牛奶製品、肉類/肉類製品等，若食物保⬀不當，沙門氏菌易在高溫下大量繁殖，更易傳播。少數散發病例為接觸寵物而感染，有一些群突發與被污染的生菜或水果有關。農場的動物因食用被污染的飼料而感染，而在飼養或屠宰過程中散播病菌。人與人之間糞口傳染途徑也很重要，特別是在病人腹瀉時，如果是嬰兒或糞便失禁的成人，其傳染力比無症狀帶菌者更高。

**Campylobacter**
1. 曲狀桿菌通常發現於野生或飼養的牛、馬、綿羊、山羊、猴子、豬、狗、貓和各種禽鳥類之腸胃道，大量動物宿主是人感染來源。
2. 感染動物的排泄物可能污染土壤或水，又感染動物於屠宰過程其腸道內病菌常污染肉類。多數人感染途徑是由於食用污染之食品，如未煮熟家禽、肉品和未經適當滅菌之牛奶和水。
3. 在廚房處理受感染之雞肉、鴨肉，使用同一個砧板處理其他菜類也可能引起感染。
4. 直接接觸感染動物包括農場動物、寵物（狗、貓）和屠宰場動物也可能造成感染。

Ref: 美國疾管局 Campylobacteriosis and salmonellosis http://wwwnc.cdc.gov/travel/yellowbook/

## Question 108:

為降低醫療機構內多重抗藥性病原之交叉感染，疾病管制署響應世界衛生組織(WHO)之倡導醫護人員手部衛生運動。有關手部衛生，下列㔀述何者正確? (應選出所有正確答案)

(1) 依文獻及實驗顯示，使用酒精性乾洗手液進行手部衛生，在清潔效果、使用時機、花費時間、對皮膚的影響、安全性考量及洗手遵從性等方面，均比使用肥皂或液態皂進行濕洗手的效果為佳。
(2) WHO 推動的醫護人員手部衛生運動，強調醫護人員在手部無明顯髒汙時，優先使用酒精性乾洗手液清潔手部，乾洗手之洗手技術全程需 40-60 秒。
(3) 手部有明顯髒污或沾有血液/體液時，建議使用肥皂和清水之濕洗手技術洗手。
(4) 為提高手部衛生設備的可近性， WHO 宣導在照護點普遍設置或隨身攜帶酒精性乾洗手液方式，可達到符合在照護點伸手可及應有酒精性乾洗手液的目標。
(5) 為避免酒精性乾洗手液之產品酒精濃度不足，影響醫護人員執行手部衛生之成效，醫療機構於購買酒精性乾洗手液，應選擇酒精成分越高的越好。

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- A. (1)+(2)+(3)+(4)+(5)
- B. (1)+(2)+(3)
- C. (2)+(4)+(5)
- D. (2)+(3)+(4)
- E. (1)+(3)+(4)

### Correct Answer: E

(2)乾洗手以 20-30 秒，濕洗手以 40-60 秒為宜。

(5)酒精濃度以 70%-75%為佳，。酒精的濃度過大，將使細菌表面的蛋白質急速凝固，形成硬膜。這層硬膜會對細菌造成保護作用，阻止酒精進一步滲入細菌細胞質內。

Ref: 長庚醫院洗手衛教手冊

## Question 109:

發燒併血小板減少症候群 (severe fever with thrombocytopenia syndrome)在中國大陸及日本已有報告，下列何者最正確? (應選出所有正確答案)

(1) 致病原是新布尼亞病毒 (novel bunyavirus)
(2) 由長角血蜱 (Haemaphysalis longicornis)叮咬而傳播
(3) 急性期病人及屍體血液、血性分泌物具傳染性，直接接觸病人血液或血性分泌物可導致感染，因此可以人傳人。
(4) 臨床表現包括發燒、血小板減少、腸胃道症狀、多重器官功能失調，初期死亡率可達 10-30%。
(5) 該病正確名稱為 Granulocytic anaplasmosis。

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- A. (1)+(4)
- B. (1)+(3)+(4)
- C. (2)+(3)+(4)+(5)
- D. (1)+(2)+(3)+(4)
- E. (1)+(2)+(3)+(4)+(5)

### Correct Answer: D

選項(1) 正確
選項(2) 正確
選項(3) 正確
選項(4) 正確
選項(5) 錯誤，此病與顆粒細胞無形體病(Granulocytic anaplasmosis)表現相似但並未發現「嗜吞噬細胞無形體」(Anaplasma phagocytophilum)

發熱伴血小板減少綜合症（Severe Fever with Thrombocytopenia Syndrome, SFTS）為人畜共通傳染病，是由歸類於布尼亞病毒科 (Bunyaviridae) 白蛉病毒屬(Phlebovirus) 之新病毒「SFTSV (severe fever with thrombocytopenia syndrome virus)」所導致的疾病。此病疑似人類顆粒細胞無形體病(Human granulocytic anaplasmosis)，但 2009 年 6 月展開調查並未發現「嗜吞噬細胞無形體」(Anaplasma phagocytophilum)。

* 流行病學
SFTS 近幾年於中國大陸發現，主要分布於山東、江蘇、安徽、河南、湖北、遼寧等地區，依據中國大陸監測資料顯示，病例主要分佈於山區和丘陵等農村地區，極少在城市人口中發現。日本及韓國也有數例確定病例及死亡病例發生。
初期死亡率為 30%。
2009 年 6 月至 2010 年 9 月期間，6 省（河南、湖北、山東、安徽、江蘇及遼寧）的 241 名 SFTS 住院病患中有 171 例確診，其中 21 例（12%）死亡，97%患者為居住於山區或林木區的農民

* 傳染窩（reservoir）
研究顯示蜱蟲為新病毒 (SFTSV) 主要的傳播媒介，以長角血蜱 (Haemaphysalis longicornis) 為主，可寄生在家畜或寵物的體表。


* 傳染途徑
傳播途徑為藉由蜱蟲叮咬而感染，長角血蜱被認為是 SFTSV 的主要媒介。
蜱蟲主要棲息於草叢、樹林等野外環境，4 月至 10 月為活動季節，可寄生在家畜或寵物的體表。直接接觸急性期或死亡病患之血液或體液亦可能導致感染。

* 潛伏期
潛伏期約 7 至 14 天。

* 發病症狀
蜱蟲叮咬後多會出現紅腫、皮疹、水皰或瘀斑。多數有噁心、嘔吐及食慾不振等情形，以發燒伴隨血小板及白血球減少為主要症狀；少數重症患者因多重器官衰竭而導致死亡。

* 預防方法
避免在蜱蟲主要的棲息地如草地、樹林等環境中長時間坐臥。
落實個人保護措施：宜穿著淺色長袖衣褲、手套及長靴等保護性衣物，並將褲管塞進襪子或鞋子裡，以避免被蜱蟲附著叮咬。
在發熱伴血小板減少綜合症高風險地區活動時，於衣物及皮膚裸露部位塗抹衛生福利部核可之蚊蟲忌避劑 / 防蚊藥劑（含化學成份 diethyltoluamide，DEET）。
活動結束後應檢查全身是否遭蜱蟲叮咬或附著，並儘快沐浴及換洗全部衣物。
若發現遭蜱蟲叮咬，應儘速用鑷子夾住蜱蟲的口器，小心地將蜱蟲摘除，避免其口器斷裂殘留於體內，並使用肥皂沖洗叮咬處，可降低感染的機會。

* 預防接種建議
目前尚無疫苗。

* 備註
人類顆粒細胞無形體病(Human granulocytic anaplasmosis, HGA)
一種主要以蜱為媒介的傳染病，由細胞內的寄生的細菌嗜吞噬細胞無形體( Anaplasma phagocytophilum)導致。雖疾病表現與 SFTSV 極為相似，但 SFTSV並未發現 Anaplasma phagocytophilum。
臨床表現包括發熱、寒戰、頭痛、肌肉酸痛、顫抖、無力、白血球和血小板減少、與多重功能器官損害，嚴重時亦可能導致癱瘓甚至喪生。發病潛伏期為 7~14 天。此病容易誤診，應及早注意，以免錯過初期治療階段。傳播媒介主要是硬蜱屬及其它帶菌動物。具體傳播途徑尚未明瞭，然直接接觸危重病人或其它帶菌動物的血液或者體液，也有可能造成感染。目前有效的治療藥物為 tetracycline 類抗生素，rifampicin 以及 fluoquinolone 等。

Ref:
* 衛生福利部疾病管制署 官方網站
* 中國大陸衛生部辦公廳印發之《人粒細胞無形體病預防控制技術指南（試行）》

## Question 110:

世界衛生組織於 2012 年 9 月首度公布中東呼吸症候群 (Middle East Respiratory Syndrome)冠狀病毒感染症案例後，現在已在沙烏地阿拉伯、約旦、卡達、英國、德國、法國等國家陸續發現確診病例數百例，其中 80%以上集中在沙烏地阿拉伯。以下何者正確? (應選出所有正確答案)

(1)可透過呼吸道飛沫顆粒，直接或間接接觸感染者分泌物傳播，而造成群聚感染事件，醫療工作者具潛在遭受感染風險。
(2) 臨床症狀包括發燒、咳嗽、呼吸急促與呼吸困難之肺炎表現，部分病人出現腎衰竭、心包膜炎、瀰漫性血管內凝血、死亡率約 50%。
(3) 潛伏期一般為 9-12 天。
(4) 赴中東朝觀信徒及旅客應特別注意手部衛生及呼吸道防護措施。
(5) 我國列為第五類法定傳染病，醫護人員如遇「醫護人員發生不明原因肺炎」、「臨床出現肺炎且發病前 14 日內具有中東旅遊史」、「不明原因肺炎群聚事件」，應採取適當感染者管制措施，採集呼吸道及血液檢體送疾病管制署並通報法傳。

---

- A. (1)+(2)+(4)+(5)
- B. (2)+(3)+(4)+(5)
- C. (1)+(3)+(4)+(5)
- D. (1)+(2)+(3)+(4)
- E. (1)+(2)+(3)+(4)+(5)

### Correct Answer: E

選項(1) 正確
選項(2) 正確
選項(3) 依疾管署公佈之資料顯示為 14 天內，然考選部公佈之解答亦包含此項
選項(4) 正確
選項(5) 正確

中東呼吸症候群冠狀病毒（Middle East respiratory syndrome coronavirus [MERS-CoV]）為單股 RNA 病毒，屬於冠狀病毒科之 beta 亞科。此病毒與引起嚴重急性呼吸道症候群(SARS)的冠狀病毒並不相同，其特性仍在研究中。

* 流行病學
世界衛生組織於 2012 年 9 月公布全球第一例病例，其後經各國監測通報（含回溯性檢查），迄今已在中東地區、非洲、歐洲、亞洲及美洲陸續發現確診病例，絕大多數個案皆有中東旅遊史、居住史或工作史。男性多於女性，以中年人為主。
根據 2014 年 4 月 24 日 WHO 以及歐洲疾病管制中心公布之風險評估指出，2014年 3 月中旬以後，散發病例及醫院內群聚感染病例皆明顯增加，病例集中於沙烏地阿拉伯及阿拉伯聯合大公國，其可能原因包括季節性流行趨勢、加強接觸者追蹤檢驗、當地院內感控不佳等。經分析發現近期約有 75%之病例為接觸患者而感染(secondary cases)，大多數為醫護人員，多屬輕症或無症狀。此外，社區散發感染病例數亦增加，但尚無發現大規模家庭群聚事件。雖世界各地發現自中東地區輸出之病例數有增多趨勢，但並未在當地發現後續感染病例。整體看來，感染風險區域仍以阿拉伯半島地區為主。臺灣地區流行概況詳見福利衛生部疾病管制署「傳染病統計資料查詢系統」。整體死亡率依據統計資料來源約為 30~50%。

* 傳染窩（reservoir）
由於大部分 beta 亞科冠狀病毒之天然宿主為蝙蝠，且有報告於中東地區蝙蝠樣本分離出 MERS-CoV，因此初期認為蝙蝠可能為 MERS-CoV 感染源，但因樣本極少，且多數個案並無蝙蝠接觸史，故研判可能有其他宿主。近期研究進一步發現自中東當地單峰駱駝可分離出 MERS-CoV，其基因序列與自確診個案檢體分離出
之病毒基因序列高度相似。又血清學研究顯示多數當地駱駝曾感染該病毒，加上部分個案曾有駱駝接觸史，顯示駱駝為人類感染 MERS-CoV 之潛在感染源。目前尚無證據顯示其他動物可能傳播此病毒。世界衛生組織（WHO）及各國正在仍持續蒐集調查病毒來源與傳染窩等資訊。

* 傳染方式
一般冠狀病毒主要透過大的呼吸道飛沫顆粒，以及直接或間接接觸到感染者分泌物等方式傳播，但 MERS-CoV 確實傳播途徑仍不明。根據目前研究結果推測，個案可能因接觸或吸入患病駱駝之飛沫或分泌物而感染，人與人間的傳播主要以院內感染為主，但仍無持續性人傳人的現象。另曾有研究指出 MERS-CoV 病毒可在低溫(4℃)的駱駝生乳⬀活 72 小時，部分確診病例亦曾飲用駱駝乳。

* 預防
赴中東地區的民眾，請提高警覺並注意個人衛生及手部清潔，同時儘量減少至人群聚集或空氣不流通的地方活動，或與有呼吸道症狀者接觸。此外應避免前往當地農場、接觸駱駝或生飲駱駝等動物奶，以降低受感染可能性。老年人或具糖尿病、慢性肺病、腎衰竭及免疫不全等慢性病族群，更應謹慎做好適當防護措施。
自中東地區入境者，若有發燒或急性呼吸道症狀，應主動通報港埠檢疫人員，並配合檢疫及後送就醫作業，進行採檢與醫學評估；返國 14 天內，若出現呼吸道或發燒症狀，則應佩戴一般外科口罩儘速就醫，並主動告知醫護人員旅遊史。

* 臨床症狀
確定病例的症狀主要是發生急性的嚴重呼吸系統疾病，症狀包括發燒、咳嗽、呼吸急促與呼吸困難。從目前少數幾位病例的臨床資料顯示，感染者通常會有肺炎，部分病人會出現腎衰竭、心包膜炎、血管內瀰漫性凝血或死亡。

* 潛伏期
14 天 (依現有的病例資料顯示，一般為 7 天內; 也可能超過 7 天，少於 14 天)。
目前尚無證據可以知道中東呼吸症候群冠狀病毒可傳染期為何，惟從群聚感染事件發生，顯示人傳人的可能性甚高。

* 治療
目前無特殊治療藥劑，對於有症狀者，應給予症狀治療及支持性療法。

* 備註-1
101 年 10 月 3 日署授疾字第 1010101167 號公告新增「新型冠狀病毒呼吸道重症」為第五類法定傳染病及其相應之防治措施。
102 年 3 月 14 日署授疾字第 1020100343 號公告，修正「新型冠狀病毒呼吸道重症」名稱為「新型冠狀病毒感染症」。
102 年 6 月 7 日署授疾字第 1020100731 號公告，修正「新型冠狀病毒感染症」名稱為「中東呼吸症候群冠狀病毒感染症」。

* 備註-2
本法所稱傳染病，指下列由中央主管機關依致死率、發生率及傳播速度等危害風險程度高低分類之疾病：
下列傳染病分類表，業經衛生福利部公告自 103 年 8 月 8 日生效在案。


Ref:
* 衛生福利部疾病管制署 官方網站
* 傳染病防治法

## Question 111:

一位 36 歲男性，平日有嫖妓的習慣，此次因全身倦怠，軀幹及四肢出現紅疹而就醫，抽血檢驗結果血清 TPHA（Treponema hemagglutination）assay 為 1：5120，RPR（rapid plasma reagin）assay titer 為 128＋，請問此時最適當的首選醫療處置為何？

---

- A. aqueous crystalline penicillin-G（18-24MU/day）靜脈注射 10 至 14 天。
- B. 肌肉注射一劑 penicillin-G benzathine 2.4MU。
- C. 口服 doxycycline 100mg bid 治療兩週。
- D. 每週肌肉注射一劑 penicillin-G benzathine 2.4MU 連續三週。
- E. 肌肉注射一劑 ceftriaxone 500mg。

### Correct Answer: B

選項(A) 高劑量長時間，用於神經性梅毒
選項(B) 正確，初期、第二期、早期遲發性梅毒之建議
選項(C) 為 penicillin 過敏的替代療法
選項(D) 非正規用法 ?
選項(E) 來亂的


梅毒(syphilis)由 Treponemes pallidum 引起，而 T. pallidum 無法於體外進行培養，因此，臨床症狀懷疑下要診斷梅毒可藉由以下幾種可行的方式：

(1) 確立病灶檢體中 T. pallidum 的⬀在 (少用!!!)
A. 銀染色(silver stain)：但染色下的 artifact 常造成對 T. pallidum 的誤判
B. 聚合酶鏈鎖反應(PCR)：粉貴!!!
C. 使用特殊抗體標記後的免疫螢光染色法(IF stain)或免疫組織化學法(IHC method)：貴, 而且通常只於特殊實驗室中進行
D. 以上方式因為限制眾多，所以實際運用的情形相對少

(2) 血清學檢驗：分為 non-Treponemal 與 Treponemal 兩種 (主流!!!)
A. 非螺旋體試驗(Non-Treponemal test)：敏感性高!!!
* 「偵測」對抗 cardiolipin-lecithin-cholesterol 抗原(生理性抗原)的 IgG 和IgM。
* 目前最廣泛被使用的是快速血漿反應原凝集法(rapid plasma reagin, RPR)和性病研究實驗室凝集法(Venereal disease research laboratory test, VDRL)。
* ++**RPR 和 VDRL 的試驗有相似的敏感度，可用作初步篩檢及血清抗體的定量分析，也可作為評估療效用**++(titer 下降 4 倍可視為早期梅毒具有成功治療反應的證據)。
* 偽陽性：因為用於非螺旋體試驗的抗原是生理性抗原，可在其他組織中找到，因此在非梅毒的疾病，試驗也許會呈陽性反應，但滴定濃度很少會超過 1:8。常見於所有螺旋體門(Spirochaetales)包括 Leptospira, Borrelia, Treponema、其他細菌/病毒/病原體、自體免疫疾病、發炎、癌症、老年等。
B. 螺旋體試驗(Treponemal test)：特異性高!!!
- 用來「確認」非螺旋體試驗的陽性反應結果。
- 目前常使用的有螢光螺旋體抗體吸收試驗(FTA-ABS)和梅毒螺旋體抗體血液凝集試驗(Treponema pallidum haemagglutination assay, TPHA)。
TPHA = TPPA (Treponema pallidum particle agglutination assay)
- ++**FTA-ABS 和 TPHA 的特異性都很高，當用作確認非螺旋體試驗的陽性反應時，對梅毒的診斷有很高的陽性預測價值**++。然而，當用作正常族群的篩檢時，這些試驗卻有達 1~2%的偽陽性。
- 最新的 ELISA 法正在成形中。
-
(3) 判讀：
A. 陰性反應：
- ++**無接觸史的人，非螺旋體試驗(RPR 或 VDRL)為陰性者，表示未受到感染**++。
- ++**螺旋體試驗(FTA-ABS 或 TPHA)為陰性者，即便有類似梅毒之黏膜皮膚病灶，亦足以排除罹患梅毒**++。
B. 陽性反應：
- RPR 和 VDRL 試驗的滴定濃度反映疾病的活性
‧ 1:4 (或以上)的滴定濃度可見於首期梅毒。
‧ 在第二期梅毒，通常到達 1:32 或更高。
- RPR, VDRL, FTA-ABS 和 TPHA 試驗對不同期別未治療的梅毒的敏感度都差不多，且對第二期梅毒都呈示陽性反應。


- 治療後有持續兩個稀釋(4 倍)或更大倍數的下降反應，是早期梅毒臨床治療成功十分重要的證據。但必須注意 VDRL 與 RPR 試驗的滴定濃度並不直接相對應，治療後的追蹤定量試驗必須僅選用其中的一種。
- 隨著早期梅毒適當治療後，非螺旋體試驗會變成陰性反應或低滴定濃度(VDRL＜1:8)的陽性反應，但螺旋體試驗仍是保持陽性反應，終身存在。
- 標準治療後，RPR、VDRL 或 TPHA 試驗在追蹤期間的滴定濃度如不降反升兩個稀釋(4 倍)或更大倍數，顯示可能治療失㓿，應小心求證，再予治療
- 少於 1%的第二期梅毒病患，VDRL 試驗在未稀釋的血清呈陰性反應或弱陽性反應，但在高倍的血清稀釋情況下卻是陽性反應，稱為 prozone 現象。
- 陽性反應的梅毒血清學檢查，只能確立病患感染，但無助於感染狀況或期別的判斷，亦不能據以斷定過去的治療效應。
C. 偽陰性反應：
- 非螺旋體的試驗對大約四分之一的首期梅毒病人呈現陰性反應。在首期梅毒的早期，如果非螺旋體的試驗結果是陰性反應，應作 FTA-ABS 試驗辨別，或在 1~2 星期後複查非螺旋體的試驗。
D. 偽陽性反應：
- 自體免疫疾病患者。
- 偽陽性反應的流行率隨年紀增加而增加，年紀超過 70 歲的人約 10%會有偽陽性反應。
- 近期曾有病毒性疾病或接受疫苗接種的人、傳染性單核球症、傳染性心內膜炎、外生殖器疱疹病患、愛滋病病毒感染患者、瘧疾患者。
- 由於臨床懷疑、或曾有接觸病史、或性傳染病風險增加的人口，或藥品注射者，會有少於 1%的篩檢試驗呈偽陽性反應。
-
(4) 臨床上，哈里遜說醫師必須在以下三種目的下熟悉運用以上那些檢驗：
- 篩檢，請選擇非螺旋體試驗 (RPR 或 VDRL)
- 診斷非螺旋體試驗陽性之疑似感染病患，請加做螺旋體試驗(FTA-ABS 或TPPA)
- 定量以判斷疾病活性或治療成效，請選擇「其中一種」非螺旋體試驗 (僅RPR 或僅 VDRL)
-
(5) 重要!!! 梅毒血清學檢查綜合判讀：
- ++**RPR 或 VDRL (-)，TPHA (-)：未感染梅毒 或 感染梅毒初期**++
- **RPR 或 VDRL (-)，TPHA (+)：已治療之梅毒感染**
- **RPR 或 VDRL (+)，TPHA (-)：非梅毒感染(偽陽性) 或 感染梅毒初期**
- **RPR 或 VDRL (+)，TPHA (+)：開始治療 或 未治療之梅毒感染**

治療梅毒，目前請依據 CDC's 2006 guidelines
(1) Penicillin G 對於 T. pallidum 至霸，即便是低濃度(也許需長期治療)
(2) 其他可選擇的有 tetracyclines, erythromycin, cephalosporin 類


Ref: Harrison's Internal Medicine, 17th ed., Chapter 162. Syphilis

## Question 112:

一位 19 歲男性，自訴為男同性戀，有多次未保護之危險性行為，最近 10 天頭痛、發燒、頸部淋巴結腫大、四肢關節酸痛而就醫，理學檢查體溫為 39.1℃，頸部僵硬觸診頸部淋巴結壓痛，多處軀幹皮疹及肝脾腫大，實驗室檢查血清學 EBV、Anti-HIV、
Mycoplasma IgM、Anti-CMV IgM 均為陰性反應。醫師懷疑病患有初期 HIV 感染，請問下列那一項試驗最能早期偵測是否有 HIV 感染？

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- A. 血液週邊單核球（PBMC）HIV 培養。
- B. 血漿病毒量 HIV RNA（RT-PCR）。
- C. 再做一次血液 Anti-HIV 抗體。
- D. 血液 HIV Western-Blot（西方墨點測試）。
- E. 血液 CD4 淋巴球數。

### Correct Answer: B

選項(A) HIV 病毒培養為診斷的選擇之一，然無文獻指出對於早期感染的診斷有貢獻
選項(B) 正確，早期感染病毒大量複製 RNA 量增加，應以偵測病毒 RNA 為方向
選項(C) 除非 seroconversion，不然再做幾次也是惘然
選項(D) 正規確立診斷的試驗，但需在 ELISA 兩次呈現陽性反應時進行
選項(E) 早期感染 CD4 T 淋巴球數量可能出現短暫的下降，但非特異性變化

診斷 HIV 感染可藉由偵測血液中的抗體或是直接偵測血液中的 HIV 顆粒或其成分。

(1) 標準「篩檢」試驗為 enzyme-linked immunosorbent assay (ELISA) = enzyme immunoassay (EIA)，偵測血清中的 HIV 抗體，敏感性極高(>99.5%)。
- 其結果常顯示為 positive (highly reactive), negative (nonreactive), 或indeterminate (partially reactive)。
- 偽陽性：⬀在抗 class II antigens 之抗體, 自體免疫, 肝病, 近期曾接受過流感疫苗注射, 及病毒感染急性期。
-
(2) 標準「確診」試驗為在 ELISA 兩次呈現陽性反應後，進行西方墨點法(the Western blot)，提供較高之特異性。
然而，對於抗體陰性臨床症狀相符合之疑似個案(也就是過去俗稱的空窗期)，早期的診斷則必須仰賴 HIV RNA 的檢測 (早期 HIV 感染之特色即為病毒 RNA 將有顯著增加的情形，當此，患者血中 CD4 T cell 數量有可能出現暫時的下降)。臨床上較常採用的方式為：**反轉錄酶聚合酶鏈鎖反應(reverse transcriptase-polymerase chain reaction, RT-PCR)**放大並偵測 HIV RNA。
- 高敏感性，高特異性
- 優於偵測分支去氧核醣核酸(branched DNA, bDNA)，擁有較低的偽陽性率。


Ref:
1. Harrison's Internal Medicine, 17th ed., Chapter 182. Human Immunodeficiency Virus Disease: AIDS and Related Disorders
2. Schwartz DH, et al. Extensive evaluation of a seronegative participant in an HIV-1 vaccine trial as a result of false-positive PCR. Lancet 1997; 350:256
## Question 113:

下列有關鉤端螺旋體感染（Leptospirosis）之㔀述，何者正確？ (應選出所有正確答案)
(1) Leptospirosis 屬於人畜共通傳染病（zoonosis），其致病原最重要的貯⬀窩（reservoir）是鼠類。
(2) Leptospira 感染人體可經由有傷口的皮膚或完整的黏膜進
入，並且可人傳人（human-to-human transmission）。
(3) Leptospirosis 感染者可以像是流行性感冒的臨床表現，出現發燒、畏寒、頭痛、肌肉酸痛等，發燒可持續 3-10天。
(4) Weil's syndrome 病人會有黃疸、急性腎功能損傷障礙、肺部出血及高死亡率。
(5) 首選藥物治療為 azithromycin。

---

- A. (1)+(2)+(4)
- B. (2)+(3)+(4)
- C. (3)+(4)+(5)
- D. (1)+(3)+(5)
- E. (1)+(3)+(4)

### Correct Answer: E

選項(1) 正確
選項(2) 錯誤，人與人間直接傳染極為罕見
選項(3) 正確
選項(4) 正確
選項(5) 錯誤，是 penicillin 及 doxycycline 類

* 致病原
鉤端螺旋體菌屬 (Leptospires) 為螺旋菌科(Spirochaetales)，致病性鉤端螺旋菌屬於 Leptospira interrogans 菌種，現今已被鑑識出之血清型約有 277 種。
* 流行病學
1. 在世界各地，不論鄉村或城市，已開發或開發中國家，除了極地之外，皆有鉤端螺旋體病發生。此病易發生於野外經常接觸可能受感染動物排泄物污染之水源或屠體組織之工作者，如：農民、礦工、獸醫、畜牧業者、漁民及軍隊等；於人群中爆發流行原因，為接觸到受感染動物污染之水源（例：河流、湖水等），尤其是在污染區從事野外活動－游泳、露營、運動等。洪水氾濫後常見爆發性流行。
2. 臺灣病例概況
臺灣於 2006、2007 及 2008 年確定病例分別為 41、42 及 47 例（共 130 例）。
2009 年因莫拉克颱風襲台，造成屏東縣萬丹鄉大淹水，造成鉤端螺旋體病群聚，該年確定病例為 203 例。
* 傳染窩
幾乎所有的哺乳類動物，包括野生和家畜動物，如鼠類、狗、牛、豬等。
* 傳染方式
為人畜共通疾病，但人與人間直接傳染極為罕見。
可經由食入或接觸受感染動物之尿液或組織污染的水、土壤、食物而感染。當人們工作（農夫、衛生下水道工程人員或維修人員、礦工）、游泳、戲水或野營時，經由皮膚傷口、口咽黏膜、眼結膜、鼻腔或生殖道的傷口感染。
* 預防
1. 勸導民眾避免在遭受污染的水中游泳或涉水。當工作必須暴露於病源環境時，採用適當的防護措施
2. 保護高危險工作者，提供長靴、手套和圍裙。
3. 避免接觸可能遭受污染的水或土壤。
4. 滅鼠，尤其是農村，保持居家環境清潔。
5. 隔離被感染的動物，避免其尿液污染環境。
6. 對畜養之動物施打預防性疫苗。
* 臨床症狀
感染者的臨床症狀不一，可能沒有症狀或產生各種症狀，從輕微到嚴重都有可能；輕微者最初的症狀多半與感冒類似，包括發燒、頭痛、腸胃道不適、畏寒、紅眼、肌肉酸痛等症狀，有的還會以腦膜炎症狀表現，嚴重者會出現腎衰竭，黃疸與出血現象。
* 潛伏期與傳染期
潛伏期通常為 1~2 週，範圍包含 2~30 天。人與人間直接傳染極為罕見，螺旋體可經由尿液排除達一個月或更長，因此病人的污物（尤其是尿液）須小心處理。
* 治療
雖然目前尚無足夠 review 證據定立臨床治療的指引，但有許多 RCT 顯示 penicillin及 doxycycline 可能為有效治療選擇。


值得注意的是少部分的病患會發生 Jarisch-Herxheimer reaction(這是一種在penicilling 使用下造成細菌內毒素釋放後造成發燒的現象)

* 備註
Weil's syndrome 即指最為嚴重的 leptospirosis，典型的表現包括黃疸(jaundice)、腎功能惡化(renal dysfunction)及出血傾向(hemorrhagic diathesis，尤
以肺部為常見)，整體死亡率可達 5–15%。

Ref:
1. Harrison's Internal Medicine, 17th ed., Chapter 164. Leptospirosis
2. 衛生福利部疾病管制署 官方網站

## Question 114:

一位 46 歲女性病人，因發燒及畏寒一週至本院急診，理學檢查發現有二尖瓣收縮期心雜音，兩套血液培養均長出 Enterococcus faecalis，對所測試之抗生素均具敏感性（susceptible），請問下列何種藥物治療方式是最合適之選擇？

---

- A. Cefazolin + gentamicin。
- B. Ampicillin + gentamicin。
- C. high dose Penicillin alone。
- D. high dose Ceftriaxone alone。
- E. Vancomycin alone。

### Correct Answer: B

大部分 Enterococcus 造成的亞急性心內膜炎幾乎都是由 E. faecalis 造成 ，雖然Enterococcus 對於低濃度的 penicillin 以及 aminoglycosides 幾乎呈現抗藥性，於許
多體外(in vitro)與體內(in vivo)的試驗中均顯示當 penicillin / ampicillin 或vancomycin 合併 aminoglycoside (例如 gentamicin)給予時能展現有效的協同作用。
因此，目前 American Heart Association (AHA)及 British Society for Antimicrobial Chemotherapy (BSAC)都建議：治療低 penicillin 抗藥性的 E. faecalis 採用靜脈注射之 aqueous penicillin G 或 ampicillin 輔加 gentamicin。而 European Society for Cardiology (ESC)則建議使用 penicillin G 或 vancomycin 輔以 gentamicin，共計 4~6
週。
雖然 ampicillin 較 penicillin 具有更強的效價，但 ampicillin+gentamycin 卻沒有獲得實
證醫學證實。

以下為針對 E. faecalis 造成之心內膜炎，綜合 AHA, BSAC, ESC 所建議之治療：


Ref:
1. Data from American Heart Association (AHA), British Society of Antimicromial Chemotherapy (BSAC), and European Society of Cardiology (ESC)

## Question 115:

有關新型流感 H5N1 及 H10N8 流感病毒感染之㔀述，下列何者為非？ (應選出所有正確答案)
(1) H5N1 與 H10N8 皆具有對人類下呼吸道 α2,3-linked sialic acid 接受器結合之能力，易造成急性肺損傷。
(2) H10N8 病毒六段內部基因來自於 H9N2 禽流感病毒。
(3) H5N1 與 H10N8 流感病毒曾在中國大陸發生人傳人群突發流行。
(4) H5N1 與 H10N8 流感病毒皆對於鳥禽類為高致病性及高致死率感染。
(5) H10N8 與H5N1 大部份病毒株對現行藥物 neuraminidase inhibitor（如 oseltamivir）均具有抗藥性。

---

- A. (2)+(4)+(5)
- B. (3)+(4)+(5)
- C. (1)+(2)+(3)
- D. (1)+(3)+(5)
- E. (2)+(3)+(4)

### Correct Answer: B

選項(1) 正確，大部分禽(avian)流感病毒對於 2,3-linked sialic acid 親和力較高
選項(2) 正確，將就記一記吧
選項(3) 錯誤，H10N8 未曾大流行
選項(4) 錯誤，H10N8 非
選項(5) 錯誤，目前無抗藥性

選項(1)
簡單的說，流感病毒造成感染必須藉由與呼吸道上的 sialic acid 結合：
- 人類呼吸道上皮：含有 2,6-linked sialic acid 較多，2,3-linked sialic acid 較少
- 禽類呼吸道上皮：含有 2,3-linked sialic acid 較多，2,6-linked sialic acid 較少
- 畜類呼吸道上皮：2,3-linked sialic acid 及 2,6-linked sialic acid 均有
然而，
- 大部分人流感病毒(human influenza)對於 2,6-linked sialic acid 的親和力較高
- 大部分禽流感病毒(avian influenza)對於 2,3-linked sialic acid 的親和力較高
- 大部分豬流感病毒(swine influenza)對於兩者均高
這也解釋了為何禽流感在人類較少造成流行(人類呼吸道上皮 2,3-linked sialic acid 較少)，而豬流感為何能夠感染人與禽鳥。
更進一步，研究顯示：要增加在人類宿主間禽流感病毒的繁殖及傳染力，病毒必須提昇與 2,6-linked sialic acid 的連結；此外，減少與 2,3-linked sialic acid 的結合也在雪貂身上被發現能增加飛沫傳染(droplet-based transmission)的機會。

選項(2)
中國疾控中心完成全球首宗人類 H10N8 死亡個案分析，病毒基因圖譜顯示 H10N8已與 H9N2 禽流感出現洗牌，六組內部基因(PB2, PB1, PA, NP, M, NS)可能源自 H9N2禽流感，其中病毒中 PB2 蛋白含量足以入侵哺乳類動物，感染下呼吸道或肺底部。
專家估計最大可能是候鳥將 H10N8 傳給鴨後，鴨與帶 H9N2 的雞隻接觸，令病毒基因洗牌，形成全新品種 H10N8 病毒。

選項(3)
僅 H5N1 於 1987(中國), 2009(中國), 2012(全世界 12 個國家)造成 pandemic。

選項(4)
H5N1流感病毒主要感染鳥類，在鳥類間的傳染性高並易致死。
病毒常常在世界各地遷徙性水鳥和海鳥的腸內容物中分離到。有相當多的證據指出遷徙的水鳥會引入病毒感染家禽。疾病一旦引入禽群，病毒藉著感染鳥移動，污染設備，蛋盒，飼料卡車，工作人員等由一個禽群傳播到另一個禽群。
禽鳥的H5N1流感疫情自2003年底至2004年初之間，在亞洲國家發生流行，並造成至少1億隻禽鳥因染病或撲殺而死亡。

選項(5)
Amantadine與Rimantadine可做為預防與治療A型流感病毒之用，只有Amantadine通過能用於治療孩童。
另一類藥物包括Oseltamivir與Zanamivir是NA的抑制物。對於A型流感病毒與B型流感病毒均有療效。Oseltamivir與Zanamivir的藥物作用是降低病毒從感染細胞內釋放出來。在感染的前兩天內使用這類藥物可有效治療無併發症的病人。
Zanamivir適用於七歲以上的人，以吸入的方式一天給兩次，共給五天。
Oseltamivir適用於一歲以上的人，口服給藥，一天兩次，共五天。

Ref:
1. Ramos I, et al. Hemagglutinin receptor binding of a human isolate of influenza A(H10N8) virus. Emerg Infect Dis. 2015 Jul
2. Ito T, et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. Journal of Virology, 72, 7367-7373 (1998)
3. Matrosovich M, et al. Early alterations of the receptor-binding properties of H1, H2, and H3 avian influenza virus hemagglutinins after their introduction into mammals. Journal of Virology, 74, 8502-8512 (2000)
4. W Qi, at el. Genesis of the novel human-infectioing influenza A(H10N8) virus and potential genetic diversity of the virus in poultry, China. Eurosurveillance, Volume 19, Issue 25, 26 June 2014

## Question 116:

有關新型流感 H7N9 感染之流行病學，下列㔀述何者錯誤？

---

- A. 根據中國大陸公佈之 H7N9 病例，感染後造成肺炎之死亡率約為 30-40％。
- B. 台灣已有境外移入之 H7N9 感染個案。
- C. H7N9 感染個案有 90％個案臨床表現為肺炎，有接近 60％為 ARDS 呼吸衰竭。
- D. H7N9 感染個案有超過 80％曾有接觸活禽史。
- E. 絕大部分 H7N9 流感藉由血清學（serology）檢定。

### Correct Answer: E

選項(A) 請背起來 XD
選項(B) 請記起來 XD
選項(C) 請內化 XD
選項(D) 請當成冷知識 XD
選項(E) 錯誤，藉由免疫螢光染色或 HI 法(hemagglutination inhibition assay)

建議直接參考 新型流感 H7N9 之相關資料(包含台灣現階段診療指引)均可於疾管署官方網站獲得：
http://www.cdc.gov.tw/professional/list.aspx?treeid=beac9c103df952c4&nowtreeid=935e03b9727da8ae

中國大陸自 2013 年 3 月 31 日起公佈全球首例人類 H7N9 流感確定病例，個案數目前仍在持續增加中，病例初期臨床症狀包含發燒、咳嗽 及呼吸短促等，重症病例之病程快速進展為嚴重肺炎，併發急性呼吸窘迫症候群、㓿血性休克及多重器官衰竭而
死亡，目前致死率約 2~3 成，陸續發現少數輕症病例。
* 致病原
H7N9禽流感病毒（H7N9 Avian Influenza virus）屬正黏液病毒科（Orthomyxoviridae），是A型流感病毒屬的一種次亞型，由3種不同禽流感病毒株之基因重組而成，其中H7基因片段係源於中國大陸東部鴨科分離出之H7N3禽流感病毒，N9基因片段則與韓國野鳥流行之H7N9禽流感病毒相近，而其餘6個基因片段 （PB2、PB1、PA、NP、M、NS）則與 H9N2 禽流感病毒相近。
A型禽流感病毒除感染禽類外，還可能感染人、豬、馬、雪貂和海洋哺乳動物。禽流感病毒普遍對熱敏感，對低溫抵抗力較強，65℃加熱30分鐘或煮沸（100℃）2 分鐘以上可使病毒失去活性。該病毒在較低溫環境下的糞便中可⬀活1週，在4℃水中可存活1個月，對酸性環境具抵抗力，在pH4.0的條件下亦可存活。在有甘油
存在的環境下可保持活性長達1年以上。
* 流行病學
大部分的確定病例具禽鳥、禽鳥分泌物或排泄物、禽鳥所在環境接 觸史，尤其是曾經出入活禽市場。目前僅出現少數的家庭群聚案例，顯示 H7N9 流感病毒可能具有限性人傳人的能力，但尚無可持續性人傳人的證據。
* 傳染窩
中國大陸陸續於確定病例曾經進出之活禽市場的禽鳥及環境中檢 測到 H7N9 流感病毒，但因為該病毒感染禽鳥後不會造成明顯症狀，因 此染病禽鳥與人類病例的直接關係尚難直接證實，仍待更多實證研究。
* 傳染途徑
H7N9 流感病毒的傳染途徑尚未確立。一般來說，禽流感病毒會⬀在於染病禽鳥的呼吸道飛沫顆粒及排泄物中，人類主要是透過吸入或接觸禽流感病毒顆粒或受汙染的物體與環境等途徑而感染。
* 潛伏期與可傳染期
依現有人類確定病例之流行病學研究結果，大多數 H7N9 流感病例 的潛伏期在1~10 日之間，目前我國採用 10 日作為估計之潛伏期上限。目前尚無足夠證據推論 H7N9 流感的可傳染期，目前以個案症狀出現前 1 天至症狀緩解後且檢驗證實流感病毒陰性後為止。
* 潛伏期與可傳染期
根據現有中國大陸所公布人類感染 H7N9 流感病例的調查結果，患者一般表現為類流感症狀，如發燒、咳嗽，可伴有頭痛、肌肉痠痛、畏寒和全身倦怠。重症患者因細胞因子風暴導致全身炎症反應(Systemic inflammatory response syndrome)，其病情發展迅速，多在 3~7 天出現嚴重肺炎，體溫大多持續在 39℃以上，呼吸困難，可伴隨咳血；可能快速進展為急性呼吸窘迫症候群、㓿血性休克，甚至多重器官功能障礙。
* 診斷方法
急性感染時可由 throat swabs, nasopharyngeal washes,或 sputum 偵測到病毒。
最常使用的是快速病毒試驗(rapid viral tests)偵測 nucleoprotein or neuraminidase，敏感性可達 60–90%。反轉錄聚合酶鏈鎖反應(RT-PCR) 亦可用來偵測 nucleic acids。至於區分 A 型流感病毒屬或是 B 型流感病毒屬，甚至病毒亞型，則可使用 immunofluorescence 或 Influenza hemagglutination inhibition assay (HI assay)。
血清學檢定(Serologic methods)較為繁複，且須比較不同時段(急性期與恢復期)
病患血清中的病毒濃度，常用作回溯性(retrospective)診斷用。

Ref:
1. Harrison's Internal Medicine, 17th ed., Chapter 180. Influenza
2. 衛生福利部疾病管制署 官方網站

## Question 117:

AIDS 病患為 T 淋巴細胞功能缺損之易感受主，下列何種病原並非為此類病患常見之感染症致病原？

---

- A. Pneumocystis jirovecii。
- B. Cytomegalovirus。
- C. Herpes simplex virus。
- D. Candida albicans。
- E. Shigella flexneri。

### Correct Answer: E

常見的感染症，請參閱哈里遜Ch.182的Table 182-8 NIH/CDC/IDSA 2008 Guidelines for the Prevention of Opportunistic Infections in Persons Infected with HIV (以下為節錄重整)


Ref: Harrison's Internal Medicine, 17th ed., Chapter 182. Human Immunodeficiency Virus Disease: AIDS and Related Disorders

## Question 118:

一位 40 歲血液疾病患者，接受全脾臟切除術，（splenectomy），下列㔀述何者為非？

---

- A. 大部份感染發生於脾臟切除後的前 2 年內
- B. 重症感染之死亡率可高 50％
- C. 主要感染的致病菌為有莢膜性細菌，例如：Neisseria meningitides
- D. Salmonella 為最常見之致病原，約占 50-70％
- E. 兒童接受脾臟切除後發生感染的風險高於成人接受脾臟切除者之感染風險

### Correct Answer: D

其他選項皆為正確，
(D)選項 最常見的致病原為 pneumococcal pneumonia
其他 post splenectomy 容易造成的 complications 還包括 thrombosis

UPTODATE:
While postoperative outcomes are generally more favorable with laparoscopic approaches either
can be associated with serious complications (eg, risk of infection with encapsulated organisms [especially in the pediatric population], pneumonia, intra- and post-operative hemorrhage, thrombocytosis with or without venous thromboembolism, pancreatitis, gastric fistula, with reported morbidities and mortalities in patients with hematologic disorders ranging from 8 to 52 percent and zero to 9 percent, respectively

* **Infection**: Splenectomized patients had a significantly increased risk of pneumococcal pneumonia (RR 2.1), pneumonia not otherwise specified (RR 1.9), meningitis (RR 2.4), and septicemia (RR 3.4), as well as a significantly increased risk of death from pneumonia (RR 1.6) and septicemia (RR 3.0).
* **Thromboembolism**: Splenectomized patients had a significantly increased risk of developing deep vein thrombosis and pulmonary embolism (RR 2.2 for both), but not acute myocardial infarction, coronary artery disease, or ischemic stroke. Risks did not differ when analyzing for race, age at splenectomy, trauma, or prior autoimmune disease.
* **Malignancy**: Malignancy developed in 13 percent of the splenectomized patients during follow-up. There was a significantly increased risk of any cancer as well as death from any cancer (RR 1.5 for both). Subgroup analysis revealed an increased risk of death from cancer of the liver (RR 1.8), pancreas (RR 2.2), lung (RR 1.3), non-Hodgkin lymphoma (RR 4.7), and any leukemia (RR 2.4). Risks were similar when stratified by race, age at splenectomy, and trauma. Risks for most of the malignancies tended to be highest during the first two to five years post-splenectomy. However, after more than 10 years, there was still a significantly increased risk of esophageal, liver, and lung cancers, non-Hodgkin lymphoma, Hodgkin lymphoma, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, and any leukemia.

Ref:
Uptodate: Approach to the adult patient with splenomegaly and other splenic disorders

## Question 119:

有關社區細菌性腦膜炎感染之㔀述，何者為非？

---

- A. 成人最常見的致病菌為 Streptococcus pneumonia
- B. 60 歲以上患者或免疫缺陷患者，需考慮 Listeria monocytogenes
- C. Streptococcus pneumoniae 腦膜炎即使給予適當的抗生素治療，死亡率仍約為 20％
- D. 研究顯示 dexamethasone 10mg q6h 給予 4 天可改善成人 Streptococcus pneumoniae 腦膜炎預後
- E. 四價 Neisseria meningitidis 疫苗注射可預防 serogroup B 奈瑟氏腦膜炎雙球菌腦膜炎

### Correct Answer: E

UPTODATE:
The major causes of community-acquired bacterial meningitis in adults in developed countries are Streptococcus pneumoniae, Neisseria meningitidis, and, primarily in patients over age 50 to 60 years or those who have deficiencies in cell-mediated immunity, Listeria monocytogenes


For adults in the developed world with suspected or proven acute pneumococcal meningitis, **we recommend administration of dexamethasone (Grade 1B)**. Dexamethasone should only be continued if the cerebrospinal fluid (CSF) Gram stain and/or the CSF or blood cultures reveal Streptococcus pneumoniae.
++在 streptococcus pneumoniae 的 meningitits，Dexamethasone 需再給 antibiotic 前給，有兩種打法：一種為 0.15mg/kg Q6H 打四天，另一種打法為 0.4mg/kg Q12H 打四天++
**When indicated, dexamethasone is given 15 to 20 minutes before or at the time of antibiotic administration. Two-dose regimens are recommended: 0.15 mg/kg every six hours for four days in the developed world, based upon the Infectious Diseases Society of America guidelines, and 0.4 mg/kg every 12 hours for four days in the developing world, based upon the Vietnamese trial**.
Adjunctive dexamethasone should not be given to adults who have already received antimicrobial therapy because it is unlikely to improve patient outcomes.

Harrison (about vaccination):
Group A meningococcal polysaccharides are exceptional in that they are effective in preventing disease at all ages. Two doses administered 2–3 months apart to children 3–18 months of age or a single dose administered to older children or adults has a protective efficacy rate of >95%. The vaccine has been widely used in the control of meningococcal disease in the African meningitis belt. The duration of protection appears to be only 3–5 years.

++**There is no meningococcal serogroup B plain polysaccharide vaccine because -2,8-N-acetylneuraminic acid is expressed on the surface of neural cells in the fetus such that the B polysaccharide is perceived as "self" and therefore is not immunogenic in humans**++.

所以答案選Ｅ ，serogroup B 奈瑟氏腦膜炎雙球無有效疫苗

Ref:
* UPTODATE: Clinical features and diagnosis of acute bacterial meningitis in adults
* UPTODATE: Dexamethasone to prevent neurologic complications of bacterial meningitis in adults

## Question 120:

45 歲男性病人在健檢時發現有一 FDG-PET positive 的頸部熱點，身體檢查發現甲狀腺左側約 1 公分結節，抽血檢查free T4 正常、hsTSH 偏低，下列那一措施首先要做?

---

- A. 建議開刀切除
- B. 測Anti TPO，Antithyroglobulin Ab
- C. Fine needle aspiration (FNA) of thyroid
- D. I-131 uptake and scan
- E. 局部注射酒精

### Correct Answer: D

根據流程圖可以獲得答案，要先分是HOT nodule 或是 Cold Nodule


Ref: Harrison's Principles of Internal Medicine, 18ed, Chapter 341 Disordor of thyroid gland

## Question 121:

63 歲女性因乳癌做術前評估發現血液 BUN 24 mg/dl、Cr 1.1 mg/dl、Ca 11.1 mg/dl、 P 3.5 mg/dl、Alb 3.9 g/dl、iPTH 96 pg/ml(10-65 pg/ml)，Bone scan 正常，術後血鈣為11.3 mg/dl、iPTH 92 pg/ml、1,25 Vit D3 61 pg/ml (16-65 pg/mL)、Urine Ca 362 mg/day，下列何者為高血鈣原因?

---

- A. 乳癌轉移
- B. 異位性 PTH分泌
- C. 原發性副甲狀腺高能症
- D. 乳癌過度進行 1α hydroxylation
- E. 家族性低尿鈣高血鈣症

### Correct Answer: C

Paraneoplastic syndrome造成hypercalcemia 主要有三種可能
1. 異位性分泌PTHrP造成local osteolysis (Metastatic lesions to bone are more
likely to produce PTHrP than are metastases in other tissues)
2. 1,25-dihydroxyvitamin D的製造上升，導致腸胃道的鈣吸收增加(發生在
granulomatous disease與lymphoma)
3. 腫瘤分泌的osteolytic的cytokine或inflammatory mediators

A 跟 B 選項，如果hypercalcemia 為paraneoplastic syndrome造成的，上升的應該是PTHrP, iPTH 會被高鈣抑制, 所以反而會是hypercalcemia, low iPTH

D選項應該是lymphoma 才會

E選項 Familiar hypocalciuric hypercalcemia， FeCa<0.01，Urine calcium 要<200mg/day，題目病人的尿鈣反而是高的

Ref: Harrison's Principles of Internal Medicine, 18ed, Chapter 100 Paraneoplastic Syndromes: Endocrinologic/Hematologic: Introduction

## Question 122:

47歲女性加拿大回國僑胞因體檢發現TSH 4.5μU/m，l 甲狀腺超音波有多顆0.5-0.7cm 結節而就診，甲狀腺觸摸比正常稍大、稍硬，抽血檢查Anti TPO 242 IU/ml (< 10 IU/mL)，下列那項TSH 濃度以上，你會開始thyroxine 治療？

---

- A. 1.5 μU/ml
- B. 11.5 μU/ml
- C. 7.5 μU/ml
- D. 3.9 μU/ml
- E. 18 μU/ml

### Correct Answer: B

這題考subclinical hypothyroidsm何時要治療？

**Autoimmune Hypothyroidism**

Classification
Autoimmune hypothyroidism may be associated with a goiter (Hashimoto's, or goitrous thyroiditis) or, at the later stages of the disease, minimal residual thyroid tissue (atrophic thyroiditis). Because the autoimmune process gradually reduces thyroid function, there is a phase of compensation when normal thyroid hormone levels are maintained by a rise in TSH. Though some patients may have minor symptoms, this state is called subclinical hypothyroidism. Later, unbound T4 levels fall and TSH levels rise further; symptoms become more readily apparent at this stage (usually TSH >10 mIU/L), which is referred to as clinical hypothyroidism or overt hypothyroidism.

一開始甲狀腺功能低下，TSH會代償性的上升來維持正常的甲狀腺功能(subclinical hypothyroidsm)，可是當TSH上升到一定程度(通常>10mIU/L)，clinical hypothyroism 就會出現。

**Subclinical Hypothyroidism**

By definition, subclinical hypothyroidism refers to biochemical evidence of thyroid hormone deficiency in patients who have few or no apparent clinical features of hypothyroidism. There are no universally accepted recommendations for the management of subclinical hypothyroidism, but the most recently published guidelines **do not recommend routine treatment when TSH levels are below 10μU/ml**. It is important to confirm that any elevation of TSH is sustained over a 3-month period before treatment is given. As long as excessive treatment is avoided, there is no risk in correcting a slightly increased TSH. Moreover, there is a risk that patients will progress to overt hypothyroidism, particularly when the TSH level is elevated and TPO antibodies are present. Treatment is administered by starting with a low dose of levothyroxine (25–50 g/d) with the goal of normalizing TSH. If thyroxine is not given, thyroid function should be evaluated annually.

Ref: Harrison's Principles of Internal Medicine, 18ed, Chapter 341 Disorders of the Thyroid Gland

## Question 123:

32 歲女性因腹痛在急診照腹部電腦斷層發現 1.5公分左側腎上腺瘤(3.5 Hu)，她體重穩定，BMI 31.2 Kg/M2，3 年前發現高血壓，目前服用 Amlodipine 10 mg qd，Ramipril 10 mg qd；血壓144/82 mmHg，抽血(4PM) Na 143 meq/L、K 3.6 meq/L，plasma metanephrine正常，plasma aldosterone 6.9 ng/dl，plasma renin activity (PRA) < 0.6 ng/ml/hr，overnight Dexamethasone suppression test cortisol 0.8 μg/dl，下列那一措施最佳？

---

- A. 檢查 midnight cortisol
- B. 重檢8AM plasma aldosterone and PRA
- C. 測24 urine catecholamine
- D. 做腎上腺核磁共振
- E. 測24 urine cortisol

### Correct Answer: B

這題是要問 adrenal incidentoloma

因其他原因接受檢查，意外發現的腎上腺腫瘤稱為腎上腺偶見瘤。對這些腎上腺偶見瘤的診斷及處置，已成為臨床上 必需面對的挑戰。雖然大部份的腎上腺偶見瘤，均屬無功能的良性腫瘤，但仍有 少部份是屬於功能性腫瘤例如皮質醇分泌腺瘤、嗜鉻細胞瘤、原發性多醛酮症等，或更少見的腎上腺皮質癌，需要早期診斷及治療

流程如下： 1.詢問病史及理學檢查。2.內分泌檢查：包括上午 8 時和下午 4 時血清皮質醇 ( cortisol ) 濃度、隔夜 l 毫克 dexamethasone 抑制試驗 ( over-night 1mg dexamethasone supression test )、24 小時尿液 metanephrines 和 catecholamines 濃度、血清鉀離子濃度、血漿醛酮 素( plasma aldosterone ) 和血漿腎素活性 ( plasma renin activity, PRA ) 之濃度。3.安排磁振造影檢查。若已知有惡性腫瘤合併多發性轉移者，則略過不做上述評

(A)跟(E)都是**Cushing syndrome screening 的test， screening可以做24 urine cortisol、midnight cortisol (plasma or saliva)、及overnight Dexamethasone suppression test**
其中實驗室的檢查以 **overnight Dexamethasone suppression test** 最可靠。
當血中糖皮醇在抑制試驗 後，其指數低於 3μg/dL 以下，即可排除糖皮醇過度分泌瘤的可能性。至於 檢查上、下午的糖皮醇濃度比較，並無一致性的結論，篩檢時應可省略，也不須再加測，故A 與 E不選

(B) 當腎上腺偶見瘤病患出現有高血壓時，不論其血鉀過低或正常，必需對原發性多 醛酮症的可能性作篩檢試驗。其中建議使用敏感性及特異性極高的 ambulatory morning plasma aldosterone concentration ( PAC ) to plasma renin activity ( PRA ) ratio 來作初步的篩檢。當 PAC ( ng/dL ) / PRA ( ng/mL/hr ) 的比值大於或等於 20，或者 PAC 大於或等於 15 ng/dL 者，即可高度懷疑原發性多醛酮症的可能性 ，此時再進行姿態性刺激試驗確定醛酮素過度分泌腺瘤之診斷。

可是本題的病人有吃 ACEI，可能會導致false negative result的機會，可能因為這樣他建議重作。

Diagnostic screening for mineralocorticoid excess is not currently recommended for all patients with hypertension, but should be restricted to those who exhibit hypertension associated with drug resistance, hypokalemia, an adrenal mass, or hypertension before the age of 40 years. The accepted screening test is concurrent measurement of plasma renin and aldosterone with subsequent calculation of the aldosterone-renin ratio (ARR); serum potassium needs to be normalized prior to testing. Stopping antihypertensive medication can be cumbersome, particularly in patients with severe hypertension. Thus, for practical purposes, ++**in the first instance the patient can remain on the usual antihypertensive medications, with the exception that mineralocorticoid receptor antagonists need to be ceased at least 4 weeks prior to ARR measurement. The remaining antihypertensive drugs usually do not affect the outcome of ARR testing, except that -blocker treatment can cause false-positive results and ACE/AT1R inhibitors can cause false-negative results in milder cases**++

(C) 測量pheochromocytoma 可以測 24 urine catecholamine 或plasma metanephrine，但以 plasma metanephrine sensitivity 99%較準確，故可以不必再驗 24 urine catecholamine


Ref: Harrison's Principles of Internal Medicine, 18ed, Chapter 342 Disorders of the Adrenal Cortex

## Question 124:

76 歲女性因跌坐地上致 T11壓迫性骨折來診，她有高血壓及食道逆流服藥控制，母親在70 多歲時二側大腿骨折，她每天服用鈣片 1000 mg 並使用多種維他命，她主訴已經矮了5-6 公分，體檢發現有些駝背外無其他異常，抽血檢查 25 Vit D 33 ng/ml (15-80 ng/ml)、iPTH 32 pg/ml (10-65 pg/ml)，生化檢查及電解質皆正常，您認為最好的治療是?

---

- A. oral bisphosphonate
- B. 增加口服鈣片
- C. 皮下注射 rh PTH
- D. 使用Nasal calcitonin
- E. 增加Vit D 劑量

### Correct Answer: C

(A) 雙磷酸鹽類看起來也是治療 osteoporosis 的好選擇，不過在這題裡不像rhPTH一樣可以增bone mass，降低compression fracture造成的deformity
**biphosphate adverse effect: esophagitis 因病患原本就有食道逆流,所以不適用

(B) 各年齡鈣質建議攝取量


(C) rhPTH 使用 3-2-1 rule ( T score<-3, 2 fracture,1 new fracture)
Although chronic elevation of PTH, as occurs in hyperparathyroidism, is associated with bone loss (particularly cortical bone), **PTH also can exert anabolic effects on bone. Consistent with this, some observational studies have indicated that mild elevations in PTH are associated with maintenance of trabecular bone mass.** On the basis of these findings, several clinical trials have been performed using an exogenous PTH analogue (1-34hPTH; teriparatide) that has been approved for the treatment of established osteoporosis in both men and women. The first randomized controlled trial in postmenopausal women showed that PTH, when superimposed on ongoing estrogen therapy, **produced substantial increments in bone mass (13% over a 3-year period compared with estrogen alone) and reduced the risk of vertebral compression deformity**.

(D) Calcitonin is not indicated for prevention of osteoporosis and is not sufficiently potent to prevent bone loss in early postmenopausal women. Calcitonin might have an analgesic effect on bone pain, both in the subcutaneous and possibly in the nasal form.

(E) The Institute of Medicine recommends daily intakes of 200 IU for adults <50 years of age, 400 IU for those 50–70 years, and 600 IU for those >70 years. Multivitamin tablets usually contain 400 IU, and many calcium supplements also contain vitamin D. Some data suggest that higher doses (≥1000 IU) may be required in the elderly and chronically ill.

所以此題選(C)

Ref: Harrison's Principles of Internal Medicine, 18ed, Chapter 354 Osteoporosis

## Question 125:

25 歲女性因肥胖及糖尿病症惡化來診，目前BMI 42 Kg/M2，18 歲時被診斷第2 型糖尿病，起先用飲食控制，直至 2 年前須使用metformin，HbA1C 4 個月前為7.2%，最近因皮疹使用類固醇，體檢發現身體有多處乾癬疹塊，血壓150/85 mmHg，無其他特殊發現，抽血空腹血糖 204 mg/dl、HbA1C 9.5%，下列那一措施最重要?

---

- A. 腹部電腦斷層
- B. 測8AM cortisol
- C. 測血清 ferritin 及TIBC
- D. 測Anti-insulin及glutamic acid decarboxylase Ab
- E. 轉介做胃繞道手術

### Correct Answer: B

這題我不太知道想問什麼，後來血糖控制不好的原因很可能是使用steroid造成的因為之前使用類固醇所以check 8am cortisol level 看是否被抑制

(D)選項的anti-insulin，跟glutamic acid decarboxylase(GAD)是在type I DM 的機轉跟此題無關

Islet cell autoantibodies (ICAs) are a composite of several different antibodies directed at pancreatic islet molecules such as GAD, insulin, IA-2/ICA-512, and ZnT-8, and serve as a marker of the autoimmune process of type 1 DM. ++**Assays for autoantibodies to GAD-65 are commercially available. Testing for ICAs can be useful in classifying the type of DM as type 1 and in identifying nondiabetic individuals at risk for developing type 1 DM**++. ICAs are present in the majority of individuals (>85%) diagnosed with new-onset type 1 DM, in a significant minority of individuals with newly diagnosed type 2 DM (5–10%), and occasionally in individuals with GDM (<5%). ICAs are present in 3–4% of first-degree relatives of individuals with type 1 DM. In combination with impaired insulin secretion after IV glucose tolerance testing, they predict a >50% risk of developing type 1 DM within 5 years. At present, the measurement of ICAs in nondiabetic individuals is a research tool because no treatments have been approved to prevent the occurrence or progression to type 1 DM. Clinical trials are testing interventions to slow the autoimmune beta cell destruction.

(A)選項一下子就跳到abdominal CT太快了

(B)懷疑cushing syndrome根據流程圖要先測：
1. 24 hours free cortisol
2. Dexamethasone overnight test
3. Midnight cortisol level (saliva or plasma)

題目只說要測 8AM cortisol 我覺得有點簡單
(C)跟(E)選項不太可能

所以這題答案選(B)


Ref:
* Harrison's Principles of Internal Medicine, 18ed, Chapter 344 Diabetes mellitus
* Harrison's Principles of Internal Medicine, 18ed, Chapter 339 Disorders of the Adrenal Cortex

## Question 126:

37 歲男性主訴因下肢無力早上無法起床，但到了早上 10 時就自然好了。病史中病人透露近2 個月體重減輕3 公斤但食慾極佳，他否認有心悸，身體檢查血壓136/56 mmHg、脈搏 90/分、規則、甲狀腺正常大小，皮膚細緻溫暖，肌力檢查大腿肌力 4/5，上臂4/5，其餘 5/5，請問最有可能的診斷是?

---

- A. 原發性醛固酮血症
- B. 甲狀腺高能症併肌病變
- C. 甲狀腺毒性周期性癱瘓
- D. 異位性皮促素症候群
- E. 使用利尿劑減肥

### Correct Answer: C

題目陳述的都是一些甲狀腺亢進的症狀


(A) 選項主要會造成困難控制的高血壓

**(B)跟(C)都是甲狀腺亢進的現象，題目中病人也有proximal 的myopathy，不過按照題意應該是想問”因下肢無力早上無法起床，但到了早上10 時就自然好了”這個現象，所以還是會選(C)**

Thyrotoxicosis may cause ++unexplained weight loss, despite an enhanced appetite++, due to the increased metabolic rate. Weight gain occurs in 5% of patients, however, because of increased food intake. Other prominent features include hyperactivity, nervousness, and irritability, ultimately leading to a sense of easy fatigability in some patients. Insomnia and impaired concentration are common; apathetic thyrotoxicosis may be mistaken for depression in the elderly. Fine tremor is a frequent finding, best elicited by having patients stretch out their fingers while feeling the fingertips with the palm. **Common neurologic manifestations include hyperreflexia, muscle wasting, and proximal myopathy without fasciculation. Chorea is rare. Thyrotoxicosis is sometimes associated with a form of hypokalemic periodic paralysis; this disorder is particularly common in Asian males with thyrotoxicosis, but it occurs in other ethnic groups as well**.

(D) Cushing的症狀：


(E) 這應該跟題目無關

Ref:
* Harrison's Principles of Internal Medicine, 18ed, Chapter 339 Disorders of the Adrenal Cortex
* Harrison's Principles of Internal Medicine, 18ed, Chapter 341 Disordor of thyroid gland

## Question 127:

74 歲男性因倦怠、食慾差，體重減輕來診，身體檢查 BMI 17 Kg/M2、血壓130/70 mmHg、脈搏 54/min，臉部稍有浮腫，眼結膜稍蒼白，其餘無特殊發現，抽血檢查： Hb 9.0 gm/dl、WBC 4000/μl、platelet 80,000/μl、Na 125 mM、K 3.6 mM、T-CHO 260 mg/dl、LDL 145 mg/dl、BUN 35 mg/dl、Cr 1.5 mg/dl、free T4 0.6 ng/dl (0.8-2.4ng/dl)、hsTSH 0.1 μU/ml (0.4-4.2μU/ml )；大便檢查無潛血，下列處置何者最恰當？

(1) 給予3% NaCl solution
(2) 給予statin 治療
(3) 即刻補充thyroxine 125μg/day
(4) 測定8AM cortisol、ACTH
(5) 做sella MRI

---

- A. (1)+(2)
- B. (2)+(3)
- B. (3)+(4)
- D. (4)+(5)
- E. (1)+(5)

### Correct Answer: D

General weakness, poor appetite, BWL and hyponatremia, 臉腫 -> consider adrenal insufficiency

Dyslipidemia, low free T4, low TSH: consider hypothyroidism

合併兩種則考慮 Panhypopituitarism

(1) 不適合,因為沒症狀
(2) 若為hypothyroidism造成的hyperlipidemia, 則是治療甲狀腺低下
(3) 錯誤 , 若為panhypopituitarism 則要先補充glucocortoicoid, 若單獨補充甲狀腺素可能會造成 adrenal crisis
(4) 懷疑adrenal insufficiency
(5) 懷疑Panhypopituitarism

## Question 128:

50歲中年男性主訴陽萎來診，身體檢查BMI 27 Kg/M2、血壓140/90 mmHg，其餘無特別發現，下列那些荷爾蒙檢查最適當？

(1) FSH
(2) LH
(3) Testosterone
(4) prolactin
(5) Dehydroepiandrosterone (DHEAS)

---

- A. (1)+(2)+(3)
- B. (2)+(3)+(4)
- C. (3)+(4)+(5)
- D. (1)+(4)+(5)
- E. (1)+(2)+(5)

### Correct Answer: B

50 yr old male with impotence-> thinking of andropause, and hypogonadism, secondary
* check **testosterone** for andropause, secondary hypogonadism
* check **prolactin** to rule out hyperprolatinemia induced hypotesteronemia
* check **LH** ( more specific than FSH) due to hyperprolactinemia (which suppresses LH release via a neuroendocrine pathway)
* In young men with testicular failure and Testsosterone defficiency, the reduction in T mediated neg f/back causes LH to surge
* DHEAS: usually used in hyperadrogenemia in woman, small children: congenital adrenal
hyperplasia (CAH) =>excessive DHEA-S production.

Testosterone is produced by the Leydig cells of the testicles.
There is a natural decline in the Leydig cell mass in the aging male with a concomitant decrease in testosterone production. However, secondary hypogonadism may result from hypothalamic-pituitary dysfunction and must be ruled out in the workup of the older male patient.
A small percentage of men with low testosterone will have a pituitary abnormality and can be diagnosed with LH and prolactin measurements.Low LH secretion may indicate pituitary dysfunction at the genetic or molecular level, a space-occupying lesion within the sella turcica, or a hyperfunctional pituitary adenoma resulting in hyperprolactinemia (which suppresses LH release via a neuroendocrine pathway).
The measurement of prolactin is used to rule out prolactinoma, a benign tumor of the pituitary gland that secretes the hormone prolactin.

* Hyperprolactinemia impairs the pulsatile LH release, which results in a decrease of serum testosterone secretion.
* In young men with testicular failure and T defficiency, the reduction in T mediated neg f/back causes LH to surge.

## Question 129:

25歲女性因體檢發現高血壓來診，家族史母親因甲狀腺腫開刀後，目前使用thyroxine 補充，父親亦有高血壓，於某次車禍開刀中死亡，一個姊姊因副甲狀腺高能症開刀，身體檢查發現血壓160/100 mmHg、脈搏 72/min，甲狀腺有grade1腫大，餘者無特別發現，下列措施何者最適當？

(1) 測定Na、K、Cl
(2) 測定plasma aldosterone及plasma rennin activity
(3) 測定Urine metanephrine
(4) 測定Alb、Ca、P、iPTH
(5) 做RET oncogene檢查

---

- A. (1)+(2)+(3)
- B. (2)+(3)+(4)
- C. (3)+(4)+(5)
- D. (1)+(4)+(5)
- B. (1)+(2)+(5)

### Correct Answer: Ｃ

Young age hypertension-> thinking of secondary hypertension such as pheochromocytoma
Family Hx: thyroid and parathyroid tumor -> thinking of MEN-II A(3 C)
**C**alcitonin: thyroid medullary cancer
Hypre**C**alcemia: hyperparathyroidism
**C**atecolamin: pheochromocytoma


(3)(5): urine metanephrine=> pheochromocytoma
RET oncogene=> MEN-II gene mutation

## Question 130:

58歲男性，有13年糖尿病史及長期CAD，5年前放置支架，目前使用藥物有sulfonylurea、metformin、hydrochlorothiazide、ACEI及Aspirin、atorvastatin。最近1年他加強飲食及運動，減重4公斤，體檢發現血壓126 / 72 mmHg，BMI 30 Kg/M2，腰圍99公分，其他正常；抽血HbA1C 7.0 %、CHO 174 mg/dl、LDL 66 mg/dl、TG 376 mg/dl，urine ACR (microalbumin creatinine ratio) 25μg/gm，下列哪一種治療最恰當：

---

- A. Fenofibrate
- B. Pioglitazone
- C. Insulin glargine
- D. Low carbohydrate diet
- E. Exenatide

### Correct Answer: A

TG keep< 250mg/dL-> add fenofibrate

病患因運動後血糖控制穩定，不需再加血糖藥物or diet control

Exenatide: GLP-1 receptor agonist, suppress inappropriately elevated glucagon secretion and slow gastric emptying, reducing fasting and postgrandial glucose.

## Question 131:

80 歲男性因倦怠來診，身體檢查︰BMI 26 Kg/M2，血壓140 / 90 mmHg，下肢有輕微水腫，餘無特殊發現，抽血檢查Cr 2.5 mg/dl、GOT 30u/L、GPT 25u/L、HbA1C 7.8%、glucose AC150 mg/dl，尿檢protein(++)，除了生活型態、飲食控制外，何者最適宜？

---

- A. 初發現糖尿病以胰島素注射為佳
- B. Metformin
- C. Pioglitazone
- D. Linagliptin
- E. Glimepiride

### Correct Answer: D

* Glimepiride是長效型，在腎功能不好病人較易有低血糖病發症，由cytochrome P2C9代謝 ( from Micormedex)
* Metformin, Pioglitazone 不適合因腎功能不佳及水腫
* 初發現糖尿病以胰島素注射為佳->沒有説初期打胰島素比較好

## Question 132:

29 歲女性有10 年第1 型糖尿病病史來診，最近1-2 年HbA1C 7～8%，眼底檢查過數次但都說正常，目前使用飯前短效及睡前Insulin glargine(Lantus)，每星期仍有3-4 次輕微低血糖，其他藥物只有避孕丸，身體檢查 BMI 22 Kg/M2，血壓125/75 mmHg，左眼眼底有一 microaneurysm 周邊神經檢查正常，抽血 HbA1C 7.4%，CHOL 156 mg/dl、LDL 95 ng/ dl、TG 78 mg/ dl、urine ACR (microalbumin creatinine ratio) 45 μg/gm，您的建議是：

---

- A. 即刻給予 ACEI
- B. 即刻給予 ARB
- C. 回診做尿液感染篩檢
- D. 4-6 星期後再做urine ACR 檢查
- E. 停止口服避孕丸改用其他避孕措施

### Correct Answer: D

A/B. blood pressure normal, no need of ACEI or ARB

C. no infection sign

E. no need of discontinuation of oral contraceptives

Type I DM proteinuria
Moderately increased albuminuria (formerly, microalbuminuria) is defined as persistent urinary albumin excretion between 30 and 300 mg/day (20 to 200 mcg/min). Severely increased albuminuria (formerly, macroalbuminuria) refers to albumin excretion above 300 mg/day (200 mcg/min).

* Moderately increased albuminuria generally develops 5 to 15 years after the onset of type 1 diabetes.
* Risk factors associated with the development of moderately increased albuminuria include increased albumin excretion at baseline, poor glycemic control, hypertension, presence and severity of retinopathy, and elevated total or LDL-cholesterol.
* Moderately increased albuminuria increases the risk for developing severely increased albuminuria, retinopathy, and neuropathy and increases overall mortality.
* The preferred screening strategy for moderately increased albuminuria is measurement of the urine albumin-to-creatinine ratio in an untimed urinary sample. A value of 30 to 300 mg/g of creatinine suggests that albumin excretion is between 30 and 300 mg/day and therefore that moderately increased albuminuria is probably present.
* We recommend that the albumin-to-creatinine ratio be measured yearly in all patients who have had type 1 diabetes for five years or more. An elevated ratio should be confirmed with at least two additional tests performed over the subsequent **three to six months**, with confirmation of the diagnosis requiring at least two of three positive samples.

Ref: Uptodate.

## Question 133:

62 歲男性有中風、心房顫動、高血壓病史，父親56 歲時死於心肌梗塞，弟弟58 歲因冠心症做繞道手術，他因高膽固醇血症服用Simvastatin、Atorvastatin 都 因肌肉酸痛無法使用，他也因潮紅無法使用Niacin、gemfibrozil (Lopid)造成腸胃不適，目前使用藥物為 imipramine hydrochloride (Tofranil)、Lisinopril、Diltiazem、Warfarin及diuretic，體檢發現血壓 114/71 mmHg、BMI 30.4 Kg/M2、腰圍102 公分，二側頸動脈雜音，左側偏癱，抽血空腹血糖 98 mg/dl、TSH 2.7 μU/ml、CK 57 U/L、CHO 304 mg/dl、LDL 218 mg/dl、TG 258 mg/dl、HDL 34 mg/dl，下列那一個措施是最佳的第一步？

---

- A. 給予Bezafibrate
- B. Therapeutic lifestyle change Diet
- C. 給予rosuvastatin (Crestor)
- D. 給予Ezetimibe
- E. 給予Pravastatin

### Correct Answer: Ｅ

* lower myopathy risk: Pravastatin and fluvastatin
(Ref: JAMA. 2004;292(21):2585. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.)
* Pravastatin and pitavastation has lower CAD event
* Ezetimibe: 減緩小腸對膽固醇再吸收，比任何一種statin效果都差

## Question 134:

ACCORD、ADVANCE、VADT 臨床試驗發現嘗試降低 HbA1C 接近 6% 或 6.5%，反而造成死亡率上升，最主要原因何在?

---

- A. 剌激胰島素分泌誘發癌症發生
- B. 心肌梗塞發生率增加
- C. 腦卒中發生率增加
- D. 低血糖致心律不整發生率增加
- E. 病人抵抗力降低

### Correct Answer: Ｄ

Intensive therapy — Although the association described above suggests that improvements in glycated hemoglobin (A1C) values may reduce cardiovascular outcomes, to date, most randomized clinical trials have not demonstrated a beneficial effect of intensive therapy on macrovascular outcomes in type 2 diabetes. The Veterans Affairs Diabetes Trial (VADT), Action to Control Cardiovascular Risk in Diabetes (ACCORD), and Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trials described below were designed to study the effects of intensive versus conventional therapy on cardiovascular outcomes in subjects with long-standing diabetes (duration 8 to 12 years). None show a benefit of intensive control, and results from ACCORD showed a significant increase in total and CVD mortality with intensive therapy.

VACSDM/VADT — In a feasibility trial from the Veterans Affairs Cooperative Study of Diabetes Mellitus (VACSDM), intensive insulin therapy in 153 men with type 2 diabetes (mean duration 7.8 years) was associated with an increase in the frequency of hypoglycemia and a non-significant increase in cardiovascular events. The main predictor of cardiovascular events during the study, as expected, was a history of previous CVD. However, even after correcting for baseline cardiac abnormalities, a lower A1C value was significantly correlated with an increase in new cardiovascular events.

In a longer-term prospective trial, the VADT, 1791 veterans with type 2 diabetes were randomly assigned to intensive therapy.
After 5.6 years (median), there was no difference in the first occurrence of any cardiovascular event (composite of stroke, death from cardiovascular causes, congestive heart failure (CHF), surgery for vascular disease, inoperable coronary disease, amputation for ischemic gangrene) between the intensive (achieved A1C 6.9 percent) and standard (A1C 8.4 percent) groups . In addition, there was no difference between groups in time to death from cardiovascular causes or death from any cause.
Hypoglycemia occurred more frequently in the intensive group , including episodes with impaired or complete loss of consciousness.

ACCORD — The ACCORD trial, a multicenter study of type 2 diabetes, was designed primarily to examine the effects of glycemic control, lower than had previously been achieved, on CVD in subjects with long-standing diabetes . The study cohort of 10,250 adults with a median diabetes duration of 10 years and at high risk for CVD (diagnosed with CVD or two risk factors in addition to diabetes) was randomly assigned to an intensive treatment group with the aim of achieving A1C of less than 6 percent or a standard treatment group with a A1C goal of 7.0 to 7.9 percent. The diabetes treatment strategies took advantage of an algorithmic approach using numerous diabetes medications.

In 2008, the intensive blood sugar lowering arm of the study was halted based upon a recommendation of the external Data Safety Monitoring Board due to a higher number of total and cardiovascular deaths in subjects assigned to intensive therapy .
@@@Over an average of 3.5 years, there was an excess of three deaths per 1000 subjects per year in the intensive group. However, the rate of death in both treatment groups was lower than that reported in other studies of type 2 diabetes. The primary outcome (a composite of nonfatal MI, nonfatal stroke, or death from cardiovascular causes) occurred in 352 and 371 patients in the intensive and standard therapy groups, respectively.

Extensive analyses did not identify a specific cause for the excess mortality . Subjects in the intensive group rapidly achieved target A1C values (median A1C decreased from 8.1 to 6.7 percent in four months and was 6.4 percent after 3.5 years) and experienced a greater number of severe hypoglycemic events and more weight gain than the standard group (median A1C 7.5 percent).
However, more frequent hypoglycemia did not apparently account for the difference in the death rate, nor did a specific medication or combination of medicines. Rosiglitazone, in particular, was not linked to the difference in mortality. The design of ACCORD limits the ability to determine whether the differences in glycemia between the treatment groups or the different profile of medications utilized to achieve the glycemic levels was responsible for the excess mortality.
After a mean of 3.7 years of intensive therapy, patients in the intensive therapy arm were transitioned to standard therapy and all patients were followed for cardiovascular outcomes until completion of the study (five years) . The median A1C in the intensive group remained lower than in the standard therapy group . The findings at five years were similar to those reported when the study was terminated.

* The number of total and cardiovascular deaths was higher in subjects assigned to intensive therapy . There were fewer nonfatal MIs in the intensively treated patients . The primary outcome (a composite of nonfatal MI, nonfatal stroke, or death from cardiovascular causes) occurred in 503 and 543 patients in the intensive and standard therapy groups. The reason for the higher mortality in the intensively treated patients remains unclear.

ADVANCE — The ADVANCE trial was designed to evaluate the effects of intensive glycemic therapy (based on treatment with the sulfonylurea gliclazide) and blood pressure control on CVD in patients with long-standing type 2 diabetes at high risk for vascular disease.

In the intensive glucose lowering arm, 11,140 patients were randomly assigned to either standard therapy or modified-release gliclazide plus other drugs as required to achieve an A1C of <6.5 percent. After a median of five years of follow-up, the intensive and standard groups achieved mean A1C values of 6.5 and 7.3 percent, respectively, with the A1C in the intensive group on average 0.67 percent lower.

Unlike the findings described above in the ACCORD trial, ADVANCE did not show an increased risk of death among patients receiving intensive therapy compared with standard therapy. Death from cardiovascular causes occurred in 4.5 and 5.2 percent of patients assigned to intensive and standard groups, respectively , and death from any cause in 8.9 and 9.6 percent, respectively. As in ACCORD and VADT, there was no benefit of intensive therapy on the primary composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke.

* Severe hypoglycemia occurred in more patients in the intensively treated arm . Among patients who had severe hypoglycemia compared with those who did not, the risk of a major macrovascular event, major microvascular event, and death (total and cardiovascular) was significantly increased.
The association between severe hypoglycemia and risk of a microvascular event, macrovascular event, or death was similar for patients assigned to standard and intensive glycemic control.

Ref: Uptodate.

## Question 135:

目前已知Pioglitazone之副作用包括下列各項，除了

---

- A. 水腫
- B. 心肌梗塞
- C. 肝功能變化
- D. 骨鬆
- E. 體脂增加

### Correct Answer: Ｂ

**PROactive study 證實無MI risk**

Pioglitazone 會改變體脂分佈，大腿及臀圍變多
Common adverse effect of pioglitazone
Cardiovascular: Edema (4.8% to 15.3% )
Endocrine metabolic: Weight increased
Hematologic: Anemia (less than or equal to 2% )
Musculoskeletal: Fracture of bone (5.1% ), Myalgia (5.4%)
Neurologic: Headache (9.1% )
Respiratory: Pharyngitis (5.1% ), Sinusitis(6.3% ), Upper respiratory infection (13.2% )

Serious
Cardiovascular: Congestive heart failure
Hepatic: ALT/SGPT level raised (0.3% ), Liver failure
Ophthalmic: Diabetic macular edema
Renal: Malignant tumor of urinary bladder (0.44% )
Respiratory: Pneumonia
(Ref: Uptodate.)

* PROactive trial — The largest of the trials included in the meta-analysis was the Prospective Pioglitazone Clinical Trial In Macrovascular Events (PROactive) trial, which was specifically designed to evaluate the effect of pioglitazone on cardiovascular events and mortality in 5238 patients at high risk for macrovascular complications (prior MI, stroke, coronary artery bypass graft surgery [CABG], acute coronary syndrome or symptomatic peripheral artery disease).
The study was stopped prematurely because of a significant decrease in the "main" secondary composite end point of all-cause mortality, MI (excluding silent MI), or stroke (defined after the trial was underway, and one of eight secondary outcomes) in the pioglitazone group . However, there was an insignificant impact on the predefined primary outcome of the study: composite of all cause mortality, nonfatal
MI and silent MI, stroke, acute coronary syndrome, surgical intervention on coronary or leg arteries, or leg amputation. The incidence of angina pectoris was lower in the pioglitazone group , but reports of HF were greater.

In a prespecified subanalysis of 2445 subjects with a previous MI, the addition of pioglitazone versus placebo **did not** have a significant impact on the main primary or secondary outcomes.
However, there was a decrease in the prespecified outcome of subsequent fatal/nonfatal MI in the pioglitazone group.The reduction in another prespecified endpoint, cardiovascular death or nonfatal MI (excluding silent MI), did not reach statistical significance, perhaps due to the increase in HF in the pioglitazone group .

**Edema and fluid retention**
* thiazolidinediones act by binding to and activating PPAR-gamma
Along the nephron, PPAR-gamma is most abundant in the collecting tubules, and the fluid retention with thiazolidinediones appears to result from PPAR-gamma stimulation of sodium reabsorption by sodium channels (called the epithelial sodium channel) in the luminal membrane of the collecting tubule cells
This effect is mediated by increased expression of the gamma subunit of the sodium channel gene mRNA.

**Fracture risk**
There is an increasing body of evidence suggesting that thiazolidinediones decrease bone density and increase fracture risk, particularly in women.
In animal models, treatment with rosiglitazone resulted in bone loss by suppression of osteoblast differentiation and formation. The bone loss was associated with an increase in marrow adipocytes.
In vivo studies suggest that this finding is mediated by rosiglitazone-induced activation of PPAR-gamma. PPAR-gamma2 isoform is an important regulator of adipocyte differentiation. Activation of PPAR-gamma2 results in diversion of bone marrow stromal cells from the osteoblast lineage into the adipocyte lineage, which subsequently leads to a decrease in bone formation rates and increase in adipogenesis.

The adverse impact of thiazolidinediones on bone is illustrated by the following:
In the Health, Aging and Body Composition Study (Health ABC), a four-year observational study, 666 diabetic patients, aged 70 to 79 years at baseline, had bone density assessment every two years0Although baseline bone density was similar, the subset of women (not men) taking thiazolidinediones (n = 69) had greater bone loss at the whole body, lumbar spine, and trochanter compared with those not taking thiazolidinediones.
* A Diabetes Outcome Progression Trial (ADOPT) reported a higher rate of fractures in newly diagnosed women with diabetes randomly assigned to receive four years of rosiglitazone, compared with metformin or glyburide.
* In the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes (RECORD) trial described above, the incidence of fractures was higher in the rosiglitazone group Fractures occurred mainly in the upper and distal lower limbs and were more common in women than in men.

This skeletal effect does not appear to be limited to rosiglitazone. In clinical trials of pioglitazone, there were more fractures in women (not men) taking pioglitazone than in the control groups.The fractures occurred predominantly in the distal upper or lower extremities (forearm, hand, wrist, foot, ankle, fibula, tibia).

## Question 136:

62 歲男性因急性心肌梗塞住院被發現有糖尿病，冠狀動脈攝影發現多血管疾病須進行繞道手術，病人在手術前後以Ⅳ.胰島素灌注控制血糖，住院中LVEF 為30%，無心律不整、HbA1C 12%、Cr 1.0 mg/ dl，住院中接受營養師衛教，出院前改服用 Glipizide 5 mg bid，其他藥物尚有Carvedilol 12.5 mg bid、Atorvastatin (Lipitor) 20 mg qd、Aspirin 75 mg qd、ramipril (Tritace) 10 mg qd、isosorbide 5-mononitrate (Ismo-20) 1/2＃bid、furosemide (Lasix)40 mg qd，請問治療此病人之糖尿病應如何較好？

---

- A. 停用Glipizide 改用Metformin
- B. 繼續Glipizide另加Pioglitazone
- C. 繼續Glipizide另加Metformin
- D. 繼續Glipizide另加Insulin
- E. 停用Glipizide改用Insulin

### Correct Answer: Ｅ

* Metformin 藥物不適合用在心肝腎不好的病人，易引起代謝性酸中毒
* Sulfonyl urea except metformin 會增加 CV riskà->DC glipizide
* 病患HbA1C 12%至少需 combination drugs，所以選用胰島素

## Question 137:

下列有關incretin之敘述何者正確？

(1) GIP由duodenum L cell 分泌GLP-1由IleumK cell 分泌
(2) GIP可刺激insulin 及glucagon 分泌
(3) GLP-1 可刺激insulin 分泌但抑制glucagon分泌
(4) GIP及GLP-1皆可被DDP-4分解
(5)在第2型糖尿病病人注射GIP仍可降低血糖

---

- A. (1)+(2)
- B. (2)+(3)
- C. (3)+(4)
- D. (4)+(5)
- E. (1)+(5)

### Correct Answer: Ｃ

(1) 兩者顛倒
(2) ＧＩＰ刺激insulin分泌及抑制glucagon分泌
(5) 健康人,GIP 及 GLP-1 對於胰島素刺激的 效果幾乎完全一樣,且有彼此加乘的效果。但 是在第二型糖尿病患者,只有 GLP-1 在患者的血中濃度有降低的現象,GIP 的血中濃度並無顯著異常。且只有給予患者靜脈注射之 GLP-1, 會有降低血糖的效果;給予 GIP對於第二型糖尿病的患者的血糖控制並無明顯的幫助

Ref: Uptodate. Glucagon-like peptide-1 receptor agonists for the treatment of type 2
diabetes mellitus.

## Question 138:

有關糖尿病視網膜病變之照護指引，下列何者正確？

(1) 王女士大學1 年級新生，18 歲，體檢發現為第 1 型糖尿病，須立刻做初次散瞳完整眼科檢查
(2) 李女士50 歲停經症候群，體檢發現為第 2 型糖尿病，須立即做初次散瞳完整眼科檢查
(3) 題(1)中之王女士大學畢業，初次懷孕應於 second trimester 做糖尿病視網膜檢查，並於懷孕中密切追蹤至生產後 1 年
(4) 使用Aspirin 增加視網膜出血的風險，但對保護治療心臟的病人並非禁忌
(5) 雷射光凝固法對黃斑部水腫也可減少視力喪失的風險
(6) 視網膜病變為小血管病變與病人大血管病變無關

---

- A. (1)+(2)
- B. (3)+(4)
- C. (5)+(6)
- D. (1)+(3)
- E. (2)+(5)

### Correct Answer: Ｅ

(1) 成人和10 歲以上第一型糖尿病人，在發病五年內，應接受初次散瞳的完整眼科檢查
(2) 第二型糖尿病病人在診斷後，應盡快接受初次散瞳的完整眼科檢查
(3) 初次懷孕應於第一孕期（前三個月）應做檢查
(4) 使用aspirin 並未增加視網膜出血的風險
(6) 有關

Ref: 中華民國糖尿病臨床照護指引

## Question 139:

有關糖尿病腎病變之照護指引，下列何者正確？

(1) 血壓正常下使用ACEI或ARB，對腎病變不僅無效且易有副作用
(2) 應積極治療高血壓並維持在130/80 mmHg 以下
(3) 應積極控制血糖並維持 HbA1C在6.5%以下
(4) 若病人血清肌酐酸已上升，則每三個月必須要檢查一次血清肌酐酸(creatrimine)
(5) 若病人發生巨量蛋白尿應增加蛋白質攝取( >1.0 gm/Kg )，補充流失蛋白以避免水腫
(6) 即使已是ESRD仍應積極控制血脂異常，使LDL在70 mg/dl 以下

---

- A. (1)+(2)
- B. (3)+(4)
- C. (5)+(6)
- D. (2)+(4)
- E. (1)+(5)

### Correct Answer: D

(1) ACEI or ARB對腎病變有效
(2) 正確
(3) <7.0
(4) 正確
(5) 發生巨量蛋白尿，應降低攝取至0.8g/kg/d
(6) DM+CAD LDL目標<70

Ref: 中華民國糖尿病臨床照護指引

## Question 140:

陳小姐，28 歲，未婚，因為下肢水腫來住院， 並無其他臨床表徵 (包括:雙頰紅疹、嘴破及掉髮等)，檢驗報告只有 24 小時蛋白尿3.2g， 血液白蛋白2.0 mg/dl , ANA(+)(Antinuclear antibodies) 1:1280X speckled pattern，anti-double strand DNA Ab(-) 請問接下來要做什麼檢查來診斷較為合適?

---

- A. 三天後再抽一次anti-double strand DNA Ab, 要連續3次
- B. 安排腎臟切片
- C. 安排眼底鏡檢查
- D. 抽血檢HLA typing
- E. 以上皆必要

### Correct Answer: Ｂ

按照蛋白尿的處理流程（詳見下圖），會建議病人做腎臟切片，也可以幫助ＳＬＥ病患合併有lupus nephritis的治療


Reference:
* Uptodate: Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults.
* Uptodate: Diagnosis and classification of renal disease in systemic lupus erythematosus

## Question 141:

吳小妹妹，16 歲，1 年前診斷有SLE，最近3 天媽媽發現她性格改變，開始亂罵人，又有些發燒，但無脖子僵硬，因此來住院。請問接下來要做什麼血清檢查來診斷較為合適?

---

- A. Anti-cardiolipin Ab + Anti-Ribosomal P Ab
- B. Anti-Ribosomal P Ab + Anti-Smith Ab
- C. Anti-smooth-muscle antibody (ASMA)
- D. Antithyroglobulin antibody
- E. 以上皆對

### Correct Answer: A

A. APS Ab會增加中風，癲癇，和ＭＲＩ異常發現的機會，anti-ribosomal Ab 則與depression, psychosis等中樞神經侵犯有關

B. anti-smith Ab,診斷ＳＬＥ最 specific,和疾病活動度無關

C. ASMA 和 auto immune hepatitis 有關

D. anti thyroblobulin Ab 和 autoimmune thyroiditis 有關

Ref: Uptodate. Neurologic manifestations of systemic lupus.

## Question 142:

42 歲女性病患有 primary systemic sclerosis 病史3 年，因全身抽搐被送至急診。到院時血壓200/106 mmHg，診斷為 status epilepticus。病患前一週曾至眼科門診就醫，主訴為視力模糊，眼底鏡所見為視網膜出血並有cotton wool spots。 Hb 10.1 g/dL, WBC 6450/μL, Platelets 204,000/μL, BUN 50 mg/dL, Creatinine 2.0 mg/dL, ESR 77 mm/hr, Urine protein +++, Urine RBC 10-20/HPF. 以下哪種治療最適當？

---

- A. 給予oral captopril
- B. 給予IV labetalol (Trandate)
- C. 給予oral methotrexate
- D. 給予IV phenytoin
- E. 以上皆對

### Correct Answer: A

題目暗示病人為scleroderma renal crisis, 主要特徵有1突然高血壓 2急性腎衰竭 3蛋白尿，治療主要是控制血壓，用ACEI or ARB來控制血壓為首要治療，而以captopril為最常用。

Ref: Uptodate. Renal disease in systemic sclerosis (scleroderma), including scleroderma renal crisis

## Question 143:

69 歲退休護理師，女性，類風濕性關節炎病史 15 年，於半年前接受生物製劑 adalimumab Q2W 併用methotrexate 15mg QW 及prednisolone 10mg QD治療。近三週出現疲倦、體重減輕5公斤、及夜間盜汗之情形。理學檢查並無關節發炎及DAS28 為3.1分。其他理學檢查並無皮疹淋巴腫大或肝脾腫大。胸部Ｘ光無發現異常。 Hb 13.1 g/dL WBC 7200/μL Platelets 204,000/μL RF 320 U/L ANA negative ESR 72 mm/hr CRP 5.5 mg/dL LDH及beta-2 microglobulin Both within normal ranges 請問下列何者為最適當之檢查？

---

- A. bone marrow biopsy
- B. CT scan of thorax, abdomen and pelvis
- C. PPD test
- D. QuantiFeron test for tuberculous infection
- E. Creatine kinase (CK)

### Correct Answer: D

使用免疫抑制劑後產生疲倦，體重減輕，夜間盜汗要小心ＴＢ，但症狀（B symptoms）也要小心是lymphoma，但沒有淋巴結或肝脾腫大所以比較不像，quantiferon test比PPD test準確度高，且PPD test 主要是用來檢驗latent TB infection.

Ref: Uptodate. Diagnosis of latent tuberculosis infection (tuberculosis screening) in HIV-negative adults.

## Question 144:

27 歲女性，有 5 年類風濕性關節炎病史，於1 年前開始接受生物製劑etanercept治療，目前並無關節腫痛及晨間僵硬，DAS28為2.2分。最近一個月發現臉上有紅斑及掉髮情形，臉上紅斑於日曬後更為明顯。近兩週出現左胸疼痛，尤其在吸氣時更為痛楚。請問下列何種檢查最為有診斷性？

---

- A. anti-cardiolipin antibodies
- B. anti-dsDNA
- C. anti-histone antibodies
- D. ANCA
- E. anti-SSA and anti-SSB

### Correct Answer: Ｂ

Malar rash and peri-carditis 都暗示病人可能合併有 SLE，anti-smith Ab 是診斷 SLE 最 specific 的

Ref: Uptodate. Overview of the clinical manifestations of systemic lupus erythematosus in adults

## Question 145:

下列何者不是軸心型脊椎關節炎Axial spondyloarthritis 的診斷條件之一？

---

- A. 家族史有脊椎關節炎之任一種
- B. 使用NSAID後有進步
- C. MRI有sacroiliitis
- D. ESR升高
- E. HLA-B27陽性

### Correct Answer: D

**Diagnostic classification criteria for axial spondyloarthritis, developed by Assessment of SpondyloArthritis International Society (ASAS)**
* valid for patients with back pain ≥ 3 months and age of onset < 45 years
* patients must have either of
- sacroiliitis on x-ray (grade 2 bilateral or grade 3-4 unilateral) or **magnetic resonance imaging (bone marrow edema or osteitis)** plus ≥ 1spondyloarthritis feature below
- HLA-B27 plus ≥ 2 other spondyloarthritis features below
* spondyloarthritis features
- inflammatory back pain
- arthritis
- enthesitis
- uveitis
- dactylitis
- Crohn's disease/ulcerative colitis
- psoriasis
- **family history of spondyloarthritis**
- g**ood response to nonsteroidal anti-inflammatory drugs (NSAIDs)**
- **HLA-B27**
- elevated C-reactive protein or erythrocyte sedimentation rate

Reference: Ann Rheum Dis 2009 Jun;68(6):777, editorial can be found in Ann Rheum Dis 2009 Jun;68(6):765.

## Question 146:

一位40 歲家庭主婦，因左右手脈搏強度不同而到醫院，10 年前他曾有三個月的發燒、子宮肌瘤與體重減輕之病史，當時血壓120/70 mmHg，體溫 37.8℃，脈搏80/min，皮膚沒紅斑，無口腔潰瘍，心臟無雜音，但在左邊 supraclavicular fossa有 Bruit，其他正常，10 年來她並不再看醫師，10 年前的實驗室檢查為：血比容28 %，白血球7,600/μL，血小板 480,000/μL，ESR 80 mm/hr， CRP 4.5mg/dL，CK、serum creatinine、RF、ANCA、ANA 皆陰性。這病人最有可能是何種疾病?

---

- A. Adult onset Still's disease
- B. Microscopic polyangiitis
- C. polyarteritis nodosa
- D. Rheumatoid arthritis
- E. Takayasu's arteritis

### Correct Answer: E

Positive finding
-> fever+ supraclavicular fossa有Bruit +左右手脈搏強度不同
-> PE都是血管相關的問題-> 排除A, D(症狀為關節相關)
-> BC為小血管,且B 的話ANCA 會positive -> 選E!!!

A. Adult onset Still's disease (無關節症狀因此排除此選項)
Diagnosis criteria
(Clinical)
1. fever > 2 weeks
2. evanescent nonfixed erythematous rash, and persistent arthritis > 6 weeks
for definitive diagnosis
(Ref: Bulletin on the Rheumatic Diseases1995 Apr;44(2))
(Blood tests)
1. RF(-), ANA(-)
2. ESR↑, WBC↑ (PMN > 15,000), normochromic normocytic anemia, increased liver function tests, increased ferritin 10 times upper limit of normal
(Imaging studies)
1. periarticular demineralization, characteristic fusion of carpometacarpal and intercarpal joints
(Other diagnostic testing)
1. synovial fluid WBC 10-20,000 mainly PMNs

B. Microscopic polyangiitis
Microscopic polyangiitis (MPA) is an **ANCA -associated small to medium vessel systemic vasculitis**. It is characterized by necrotizing, pauci-immune, small vessel vasculitis in the absence of granulomatous inflammation. It commonly affects the kidney and can also affect the lower respiratory tract, skin, nervous system, and gastrointestinal (GI) tract. Renal involvement can lead to glomerulonephritis and renal failure. MPA belongs to a category of vasculitides that also includes granulomatosis with polyangiitis (GPA) and Churg-Strauss syndrome

C. polyarteritis nodosa
1. definitive diagnosis should be based on signs and symptoms of vasculitis, vascular inflammation of small or medium-sized arteries on biopsy, and specific indirect evidence of vasculitis
2. no lab tests or markers specific for polyarteritis nodosa (PAN)
3. **2012 Chapel Hill Consensus Conference criteria for defining polyarteritis nodosa**
- necrotizing arteritis of medium arteries
- small arteries may be affected, but microscopic vessels not involved
- ANCA (-)
- criteria delineate a definition of PAN but are not specifically diagnostic as an individual patient may have PAN without meeting each point exactly
(Ref: Arthritis Rheum 2013 Jan;65(1):1)

D. Rheumatoid arthritis
American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria for diagnosis
1. presence of ≥ 2 typical periarticular erosions
2. presence of long-standing disease previously satisfying classification criteria
3. score > 6 on following criteria

* joint involvement (0-5)
- one medium-to-large joint – 0
- 2-10 medium-to-large joints – 1
- 1-3 small joints (large joints not counted) – 2
- 4-10 small joints (large joints not counted) – 3
- > 10 joints (> 1 small joint) - 5
* serology (0-3)
- negative RF and anticitrullinated protein antibody (ACPA) – 0
- low positive RF or low positive ACPA – 2
- high positive RF or high positive ACPA – 3
* acute phase reactants (0-2)
- normal CRP and normal ESR – 0
- abnormal C-reactive protein or abnormal ESR - 2
* duration of symptoms (0-1)
- < 6 weeks – 0
- > 6 weeks - 1

(Ref: Ann Rheum Dis 2010 Sep;69(9):1580, correction can be found in Ann Rheum Dis. 2010 Oct;69(10):1892, commentary can be found in Ann Rheum Dis 2010 Sep;69(9):1575 and in Ann Rheum Dis 2010 Sep;69(9):1577

E. Takayasu's arteritis
consider in patients < 40 years old with certain clinical finding such as
- absent or weak peripheral pulses and/or arterial bruits (most common
presenting signs)
- carotidynia (occurs in 10%-30% at presentation)
- arterial bruit
- angina
- limb claudication
- discrepancy (> 10 mm Hg) in blood pressure between upper limbs

Diagnosis generally confirmed by angiography or imaging with magnetic resonance angiography (MRA) or positron emission tomography (PET)

American College of Rheumatology (ACR) classification criteria and Chapel Hill Consensus Conference nomenclature may be used to differentiate vasculitides
* 2012 Chapel Hill Consensus Conference criteria for defining Takayasu arteritis
- granulomatous arteritis of the aorta and its major branches
- onset usually < 50 years old
(Ref: Arthritis Rheum 2013 Jan;65(1):1)

* American College of Rheumatology 1990 classification criteria for Takayasu arteritis
- age at disease onset ≤ 40 years old
- claudication of extremities, especially upper extremities
- decreased brachial artery pulse in 1 or both brachial arteries
- systolic blood pressure difference > 10 mm Hg between arms
- bruit over subclavian arteries or abdominal aorta
- abnormal arteriogram
(Ref: Arthritis Rheum 1990 Aug;33(8):1129)

## Question 147:

發炎性下背痛(Inflammatory low back pain)的特徵，下列何者為非？

(1) 發病年齡小於40 歲
(2) 漸進發生
(3) 運動過後可減輕
(4) 晨間僵硬
(5) 受傷引起
(6) high CRP

---

- A. (1)+(2)
- B. (2)+(3)
- C. (3)+(4)
- D. (5)+(6)
- E. (1)+(6)

### Correct Answer: D

發炎性下背痛應該是指 Ankylosing spondylitis, 尤以下定義可知1,2,3,4是對的

Ankylosing spondylitis
1. **chronic** inflammatory rheumatic disease primarily involving the sacroiliac joints and spine
2. men>women(2x~5x), **15-35 y/o , with 80% developing < 30 y/o**
3. prevalence estimates range from 0.1% to 2%, 0.5 and 14 per 100,000 persons/year
4. Chief concern (CC):
* back pain
- **worse upon waking or after rest**
- lasts ≥ 30 minutes
- **improves with activity**
* spinal stiffness and loss of mobility
* symptoms of anterior uveitis may include
- unilateral eye pain
- photophobia
- redness
- watering

## Question 148:

全身性紅斑性狼瘡病人須懷孕時使用下列藥物對影響胎兒最小?

(1) Glucocorticoid
(2) Tacrolimus
(3) Rituximab
(4) Cyclosporine
(5) Methotrexate
(6) Low-dose aspirin

---

- A. (1)+(2)
- B. (3)+(4)
- C. (5)+(6)
- D. (1)+(3)
- E. (1)+(6)

### Correct Answer: E

這種比較題就只好一個一個藥看了…….
(1) Glucocorticoid -> low dose 影響不大
(2 )Tacrolimus -> immunosuppresion 應該跟Methotrexate 一樣不行且Micromedex class C
(3) Rituximab -> 不行用會引起transient B-cell depletion
(4) Cyclosporine -> 第一個三月期用會引起fetal malformation
(5) Methotrexate -> immunosuppresion 因此不行
(6)Low-dose aspirin -> 可用, 生產前是否停藥尚無確切定論
-> 選1+6 (E)!!

Treatment and prevention of lupus flares during pregnancy:
1. Medications used for treatment of SLE flares during pregnancy involvement
2. initial therapy may consist of
* ++acetaminophen++ (for arthralgia)
* ++hydroxychloroquine (Class IV recommendation)++
* **non-fluorinated corticosteroids (V)**
- For mild disease activity - ++prednisone++ < 20 mg/day may be used, associated with similar risk for hypertension and diabetes as in non-pregnant women
- Increased but low absolute risk for cleft lip or palate
* immunosuppressants
- ++azathioprine++ may be safest immunosuppressant during pregnancy can be used during pregnancy at dose ≤ 2 mg/kg/day (++Class II recommendation++)

**Avoided during pregnancy** except in extenuating circumstances include
* NSAIDs
- increased risk for early miscarriage in women taking NSAIDs near time of conception
- non-selective COX inhibitors are not teratogenic, can be continued during first and second trimester (++Class I recommendation++)
- avoid selective COX-2 inhibitors during pregnancy due to lack of reliable data (++Class IV recommendation++)
- after 20 wks gestation, **all NSAIDs (except aspirin < 100 mg/day)(V)** can cause constriction of ductus arteriosus and impair fetal renal function (Class I )
- withdraw all NSAIDs except low-dose aspirin at 32 weeks gestation (Class IV )
- no consensus on when to stop low-dose aspirin before delivery
(1) some advise stopping low-dose aspirin 1 week before a planned delivery with epidural anaesthesia (++Class IV recommendation++)
(2) others do not stop low-dose aspirin in pregnant patients with antiphospholipid syndrome because they consider benefit of low-dose aspirin greater than small risk of hematoma with epidural anaesthesia (++Class II recommendation++)
* fluorinated corticosteroids (such as ++dexamethasone++ and ++betamethasone++) for treatment of flares
- transfer easily to fetus, associated with lasting adverse effects
- consider postnatal steroids for infants with in-utero exposure to fluorinated steroids only if adrenal insufficiency documented (consultation with neonatologist advised) (++Class IV recommendation++)
* ++**Rituximab(X)**++: associated with transient B-cell depletion in fetus if administered to mother in second or third trimester
* ++furosemide++: reserve for women with chronic renal failure other diuretics usually avoided due to risk for decreased intravascular volume
* ++**Cyclophosphamide(X)**++: reserve for severe lupus manifestations that have not responded to other treatments and which threaten the life of the mother and/or fetus use in first trimester associated with fetal malformation
**stop 3 months before planned pregnancy (++Class IV recommendation++)**

**Medications contraindicated for use during pregnancy** due to potential for fetal
anomalies and adverse pregnancy outcomes include
* ++leflunomide++
* ++**methotrexate(X)**++: stop 3 months before planned pregnancy (Class IV )
* ++mycophenolate mofetil++: stop at least 6 weeks before planned pregnancy because of enterohepatic recirculation and long half-life (++Class IV recommendation++)

Tacrolimus 因為dynamed裡面沒有提到所以查Micromedex 都是C級因此也不能用(X)

* U.S. Food and Drug Administration's Pregnancy Category: **Category C** (All Trimesters)
- Either studies in animals have revealed adverse effects on the fetus (teratogenic or embryocidal or other) and there are no controlled studies in women or studies in women and animals are not available. Drugs should be given only if the potential benefit justifies the potential risk to the fetus.
* Australian Drug Evaluation Committee's (ADEC): **Category C**
- Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details.

Ref:
* Dynamed : Lupus in pregnancy
* Micromedex

## Question 149:

下列藥物最常見引起紅斑性狼瘡（Lupus-like disease）為

(1) Procainamide
(2) Disopyramide
(3) Furosemide
(4) Glucocorticoid
(5) Azathioprine
(6) Methotrexate

---

- A. (1)+(2)
- B. (3)+(4)
- C. (5)+(6)
- D. (1)+(5)
- E. (1)+(6)

### Correct Answer: A

一樣就是一個一個看……..不過Dynamed上面有整理XDDD

(1) Procainamide -> definitely associated SLE(V)
(2) Disopyramide -> class Ia anti arrthymia= Quindine -> definitely associated SLE(V)
(3) Furosemide -> 不會, hydralazine 才會
(4) Glucocorticoid -> 治療用藥應該不會引起吧XDDDD
(5) Azathioprine -> 同上
(6) Methotrexate -> 同上

Drug related SLE
* drugs definitely associated: ++**procainamide (V)**++(many develop positive ANA, few develop lupus),++hydralazine++, ++isoniazid++, ++methyldopa++, ++**quinidine(V)**++, ++chlorpromazine++
* drugs probably associated: hydantoins, antithyroids (propylthiouracil), ++penicillamine++, ++lithium++, ++sulfasalazine++, beta blockers, ++quinidine++
* drugs possibly associated: ++ethosuximide++, trimethadione, estrogens, penicillin, gold salts, ++tetracycline++, reserpine, ++griseofulvin++, para-aminosalicylic acid (PAS)
* ++valproic acid++ reported to induce lupus-like syndrome in case reports
(Ref: Acta Paediatr 2008 Aug;97(8):1000)
* ++minocycline++ may be associated with lupus erythematosus
* drugs potentially associated (started within 6 months of disease development) in retrospective review of 120 Ro/SSA-positive cutaneous lupus erythematosus included ++hydrochlorothiazide++ (5 patients), ACE inhibitors (3 patients), calcium channel blockers (3 patients), interferons (2 patients) and statins (2 patients)
(Ref: Arch Dermatol 2003 Jan;139(1):45 in JAMA 2003 Apr 2;289(13):1618)