# 內專105年 151-200

## Question 151

下列有關免疫異常與罹患疾病的配對中，何者最為正確？

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- A. Complement deficiency--autoimmune disorders
- B. Antibody deficiency--frequent influenza infections
- C. Cellular immunodeficiency--chronic skin infections
- D. Phagocytic deficiency--chronic fungal infections
- E. NK cell dysfunction--carcinogenesis

### Correct Answer: A

(A) Inherited disorders of the complement system (UpToDate)
- Deficiencies in the early components of the classical complement pathway (ie, C1q, C1r, C1s, C4, and C2) predispose patients to autoimmune disorders, particularly SLE. Recurrent infections may also be seen.
- Deficiencies in late components (C3-C9) of the classical complement pathway predisposepatients to recurrent encapsulated bacteria infections, especially pneumococcal and H. influenzae (with C3 deficiency) and Neisserial infections (with C5, C6, C7, C8, or C9 deficiency).
- Partial deficiencies in complement factor H, factor I, or membrane cofactor protein (MCP)predispose to atypical hemolytic uremic syndrome (aHUS). A common polymorphism in factor H is associated with increased risk for age-related macular degeneration (AMD).

(B) Antibody deficiency :對polysaccharide antigens response缺乏，易受細菌感染，常見有 Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus

(C) Cellular immunodeficiency: infections with opportunistic organisms, such as Candida
albicans , Pneumocystis carinii , varicella zoster virus, parainfluenzae 3 virus, respiratory syncytial virus, adenovirus, cytomegalovirus, EBV, and BCG. (個人認為重點應該是伺機性感染, 不然chronic skin infections實在也不能說錯...)

(D) Phagocytic deficiency會造成chronic granulomatous disease,主要感染是Staphylococcus
aureus, Burkholderia cepacia complex, Serratia marcescens, Nocardia, Mycobacteria. (實
Aspergillus 也有提到??)

(E) 學理上來說, NK cell有抗腫瘤細胞功能, 目前也有針對利用NK cell治療癌症的研究, 但是
沒有看到有關NK cell dysfunction導致腫瘤增生的關聯性.

補充: NK cell disorders are characterized clinically by susceptibility to severe and/or recurrent infection with herpes viruses (especially varicella zoster virus [VZV], herpes simplex viruses I and II [HSVI and II], Epstein Barr virus [EBV], and cytomegalovirus [CMV]).

Ref:
- Clin Infect Dis (2014) 59 (10): 1462 - 1470. Prevention of Infections During Primary Immunodeficiency
- Journal of Allergy and Clinical Immunology. Volume 109, Issue 5, May 2002, Pages 747 – 757
- J Allergy Clin Immunol. 2013 Sep; 132(3): 515 – 526. Natural killer cell deficiency

## Question 152

下列有關全身性紅斑狼瘡患者的血清自體抗體與臨床症狀的配對中，何者最為正確？

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- A. Anti-Sm--neuropsychiatric manifestation
- B. Anti-ribosomal P--serositis
- C. Anti-SSB/La--lupus nephritis
- D. Anti-histone--drug-induced SLE
- E. Anti-RNP—vasculitis

### Correct Answer: D

附上SLE各種autoantibodies的診斷價值



(A) 有關neuropsychiatric manifestation 另一篇文獻列出以下
- anti-neuronal antibodies
- brain-lymphocyte cross-reactive antibodies
- anti-ribosomal P antibodies
- anti-phospholipid antibodies
- anti-ganglioside antibodies
(B) Serositis: anti-Sm/RNP
(C)Lupus nephritis: anti-dsDNA
(D)正確
(E)Vasculitis: Anti SSA/Ro, Anti-SSB/La

Ref:

1. Autoimmune Diseases Volume 2014, Article ID 321359, 13 pages
2. Autoimmunity. 2002 Mar;35(2):79-86. Autoantibodies in neuropsychiatric lupus
3. PLoS One. 2012; 7(2): e32001. Two Major Autoantibody Clusters in Systemic Lupus Erythematosus
4. Lupus. 2005;14(1):19-24. Pathogenic autoantibodies in lupus nephritis.
5. Medicine (Baltimore). 2006 Mar;85(2):95-104. Vasculitis in systemic lupus erythematosus: prevalence and clinical characteristics in 670 patients.

## Question 153

一位 41 歲女性為慢性肝炎患者。主訴為兩手手指及兩手肘關節僵硬、痠痛有兩個月之久。抽血檢查發現ESR 28 mm/h，CRP 1.4 mg/ml。請問下列的何種檢查對RA的鑑別診斷最有幫助？

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- A. Rheumatoid factors
- B. Complement C3 and C4
- C. ANA
- D. Anti-neutrophil cytoplasmic antibodies
- E. Anti-citrullinated peptide antibodies

### Correct Answer: E

題幹為慢性肝炎的中年女性，以上肢小關節的僵硬疼痛為表現。在關節炎的分類上，排除感染性關節炎後，要盡快排除類風濕性關節炎與乾癬性關節炎，以決定是否要及早介入以避免不可逆的關節破壞。目前認為於發病前 12 週內介入，可能對於預後有決定性的幫助。在1987 ACR對於rheumatoid arthritis的分類標準中，強調症狀應持續六周以上才能對已經確診的
RA做出可靠的分類，但其對早期疾病的敏感度有限。因此ACR與EULAR於 2010 所制定的分類標準中，已經取消症狀需大於六週的要求(但若症狀超過六週會在診斷分數上加分)，以求早期診斷並介入。 2010 類風溼性關節炎的分類標準以影響的關節數量、血清RF或anti-CCP的存在與否與數值高低、CRP或ESR的正常與否、與症狀的持續時間分別給分。


ESR是間接測量急性反應物質(acute-phase reactant)與免疫球蛋白數量的工具，其約略值為: 男性：age/2；女性：(age+10)/2，故此題的ESR數值約略偏高。Acute phase reactants是一群由肝臟在發炎時，受到IL- 6 刺激後而分泌的蛋白質，包括fibrinogen、CRP、haptoglobin、alpha- 1 - antitrypsin等等。當acute phase reactants或免疫球蛋白因為各種原因而升高後，會促使紅血球互相鍵結而加快沉澱速度。年紀、女性、肥胖、懷孕、種族等等原因都可能造成非發炎性的ESR數值上升。半衰期可能長到一週，且會受到免疫球蛋白的數量影響。CRP可以辨認磷酸等其他在細胞凋亡中釋放出的物質，並協助補體系統與吞噬細胞清除這些細胞殘渣。通常在組織受傷後 4 個小時開始上升，約 24 到 72 小時到達峰值。其半衰期約 18小時。其約略值為男性：age/50；女性：(age+30)/50，在此處的數值也有上升。

[Rheumatoid factors]
為RA的分類標準之一。為針對IgG的Fc portion的自體抗體，可為任何的抗體種類，但一般在實驗室所量測的為IgM。50%的RA病患在初診斷時體內有此抗體，而 20 - 35 的RA病患會在診斷後數個月在體內產生此抗體。RA的病人若為RF陽性，關節的破壞程度、預後、與關節外表現的風險較高。但其為不具特異性的自體免疫抗體，在慢性發炎狀態下就可能在體內出現。可以CHRONIC來做記憶：
"C"hronic disease：肝臟(primary biliary cirrhosis， 45 - 70%)、肺部(idiopathic pulmonary fibrosis， 10 -50%)、石綿沉滯症(asbestosis 30%)。
"R"heumatoid arthritis： 50 - 85%
"O"ther rheumatic disease：SLE(15-35%)、systemic sclerosis(20-30%)、MCTD(50-60%)、Sjögren's syndrome(75-95%)、polymyositis(5-10%)、sarcoidosis(15%)
"N"eoplasm：especially after radiation or chemotherapy(5-25%)
"I"nfection：AIDS/mononucleosis/parasitic infection(20-90%)、chronic viral infections(15-65%)、hepatitis B/C(20-75%)、chronic bacterial infections(如subacute bacterial endocarditis, 25-50%)、syphilis(5-13%)、mycobacterial infections(TB 8%、leprosy 5-58%)、others。
"C"ryoglobulinemia： 40 - 100%，特別是HCV相關者
此病患因有慢性肝炎病史，要考慮BC肝的可能性，故RF偽陽性的可能性較高。

[Complement C3 and C4]
在自體免疫疾病中，C3和C4的低下可能與自體免疫疾病有關。其下降的原因包括肝臟的
製造減少(先天疾病與肝臟疾病)與消耗增加(體內的免疫複合體數量上升而活化classic
complement pathway)。但其數值正常可能同時存在製造增加與消耗增加，故仍不能排除體內自
體免疫疾病的活性上升。補體的下降跟SLE、systemic vasculitis、type II & III
cryoglobulinemia、RA合併關節外表現與各種感染較為相關，但不具特異性。

[ANA]
在30%的RA病患為陽性，對診斷RA較無幫助。

[Anti-neutrophil cytoplasmic antibodies/ANCA]
在30%的RA病患為陽性，對診斷RA較無幫助。

[Anti-citrullinated peptide antibodies]
為RA的分類標準之一。Anti-citrullinated peptide antibodies為對RA最具特異性的自體抗體。在蛋白質上的Citrulline residues是透過後轉譯作用(posttranslational)的機轉形成，可在 60 -70%的RA患者體內發現，有 90 - 98%的特異性。臨床上多由synthetic cyclic citrullinated peptide來偵測，故常另稱anti-CCP antibody。可在診斷RA的數年前就在病患的體內出現，與病患的關節破壞程度有關係。可用於協助RF可能為偽陽性時的RA診斷。此題因為RF可能出現偽陽性，選Anti-citrullinated peptide antibodies對病患的正確診斷率較高。

Ref.
1. Rheumatology Secrets, 3rd edition, 2015
2. Current Diagnosis and Treatment Rheumatology, 3rd edition, 2013

## Question 154

54 歲女性患者主訴冬天時兩手多指會變白、變紫。另外臉部有蝴蝶斑、肌肉無力、及喝水時容易嗆到。身體檢查發現有香腸指及手背皮膚變硬。抽血檢查發現：C3 65 mg/mL, C4 14.6 mg/mL, ANA 1:1280 speckled + 1:640 nucleoli, RF 54 U/mL, anti-dsDNA 354 IU/mL (normal < 300 IU/mL), anti-Scl-70 < 20 IU/L, anti-RNP 2476 IU/mL, AST 121 U/mL, ALT 18 U/mL。請問最有可能的診斷為何？

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- A. MCTD
- B. SLE
- C. PSS (Progressive systemic sclerosis)
- D. RA
- E. DM/PM

### Correct Answer: A

遇冷手指變白變紫為 **Raynaud’s phenomenon** 的表現，可區分為primary(>50%)與secondary。Secondary Raynaud’s phenomenon主要的鑑別診斷包括自體免疫疾病、動脈阻塞疾病、肺高壓、神經系統疾病、血液惡病質(blood dyscrasias)、創傷、藥物等等。其中較為常見造成secondary Raynaud's phenomenon的原因是自體免疫疾病(systemic sclerosis, SLE, myositis, RA......)。初步可使用甲褶鏡作為區分，若甲褶的微血管形狀異常，即便其他症狀不明顯，也要考慮持續追蹤或早期介入。臉部蝴蝶斑為SLE表現，肌肉無力則偏向myositis或systemic sclerosis，喝水時嗆到與手背皮膚變硬則指向systemic sclerosis。香腸指一般專指dactylitis，主要的鑑別診斷包括spondyloarthritis(如乾癬性關節炎)、TB、syphilis、sarcoidosis、sickle cell anemia等等。但systemic sclerosis的早期表現包括指頭的腫脹與疼痛(puffy hands)，和dactylitis 常容易混淆。由於此病患的表現包含了systemic sclerosis、SLE、myositis的經典表現，診斷指向overlap syndrome或MCTD。

Overlap syndrome指病患的表現符合SLE、systemic sclerosis、polymyositis、 dermatomyositis、rheumatoid arthritis、或Sjögren’s syndrome這六個經典診斷的其中兩個以上稱之。在疾病的表現上，通常overlap syndrome會在兼具一種以上疾病的特徵的前提下，偏向其中一種疾病。在自體免疫疾病中，約有25%的病患會具有或逐漸表現出overlapsyndrome的特徵。

Mixed connective tissue disease(MCTD)屬於overlap syndrome的一種，其臨床表現綜合了
systemic sclerosis、SLE、polymyositis與RA，包括systemic sclerosis早期表現的Raynaud's
phenomenon(>90%)、puffy fingers(>70%)、myalgia、sclerodactyly、esophageal dysmobility，
SLE或dermatomyositis的皮疹表現，polymyositis的myositis(>50%)，RA的erosive polyarthritis，以及較無特異性的arthralgia與synovitis(>90%)等等。一般而言，MCTD幾乎不出 現嚴重的腎臟與中樞神經傷害，若有此二問題須考慮其他診斷。好發年紀為青年到中年女性 (median age 37 y/o)，其診斷需要高量的anti-U1-RNP(high titer的speckled pattern ANA)，而缺少其他特異性高的自體抗體。目前對於MCTD是否為systemic sclerosis或SLE的亞型還有爭議，但其對類固醇的反應較好，除了類似systemic sclerosis以外的症狀嚴重程度也會隨著時間
逐漸趨緩。追蹤十年後，約六成的病患診斷仍然為MCTD，有接近兩成的病患會演變成systemic sclerosis。MCTD的主要死因為肺高壓，整體而言預後較systemic sclerosis為佳。

約50%自體免疫疾病的病患在早期常無法診斷為特定疾病。Undifferentiated connectivetissue disease(UCTD)即指病患有某些自體免疫疾病的特徵與ANA，但未符合特定疾病的診斷。多數病患會有Raynaud's phenomenon(33-56%)、關節疼痛(37-86%)與synovitis。約有 30 - 50%的病患會隨著病程(約 1 - 3 年)而符合特定疾病診斷。綜合以上討論，這個病患符合overlap syndrome且有高量anti-RNP與位於邊界值的anti-dsDNA，下MCTD的診斷較為合理。

Ref.
1. Harrison’s Principles of Internal Medicine, 17th edition
2. Rheumatology Secrets, 3rd edition, 2015

## Question 155

56歲男性患者主訴為眼乾、口乾、兩側腮腺腫脹、及眼睛浮腫有三個月之久。一年前的健康檢查發現serum amylase升高，腹超檢查發現胰臟頭部腫脹及膽管、膽囊有纖維化。血清學檢查發現：anti-SSA及anti-SSB正常，ANA 1:160 speckled，Schimer’s test: OD 4mm/5min, OS: 6mm/5 min。請問下列的何種檢查對疾病的鑑別診斷最有幫助？

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- A. Serum lipase
- B. Sialoscintigraphy
- C. Anti-mitochondrial antibodies
- D. Anti-smooth muscle antibodies
- E. Serum IgG4 level

### Correct Answer: E

題幹提及的眼乾與口乾症狀為乾燥症的表現。眼睛浮腫較不具特異性，但也可為淚腺腫脹的表現。兩側腮腺的腫脹可以是Primary Sjögren’s syndrome的表現之一，但較少見於其他autoimmune disease所造成的secondary Sjögren’s syndrome。但根據2016 ACR/EULAR的Classification Criteria，Primary Sjögren’s syndrome的診斷除了乾燥症狀、相關檢查證實腺體分泌功能的異常、腺體切片證實淋巴球浸潤、與anti-SSA抗體的存在(陽性率約 50 - 70%)之外，還需要排除頭頸部放射治療、C型肝炎、AIDS、sarcoidosis、amyloidosis、GvHD、IgG4-related disease。除此之外，在有唾腺腫脹但缺乏anti-SSA與anti-SSB的狀況下(如本題)，要特別小心IgG4-related disease。唾腺腫脹的其他鑑別診斷包括：lymphoma、salivary gland neoplasm、bacterial infection(unilateral)、viral infection(bilateral)、HIV、obstruction、granulomatousdisease(tuberculosis, leprosy, sarcoidosis)......。B選項的Sialoscintigraphy只能證實有腺體功能異常，但無法協助進一步的鑑別診斷。

題幹中的amylase升高，可能是胰臟問題或是唾腺問題所造成。而腹超中所發現的胰臟頭部腫脹及膽管、膽囊有纖維化，表示膽道和胰臟有受到影響，但A選項的lipase只能提供pancreatitis的狀況，暗示胰臟受到疾病的影響，但無法提供進一步的鑑別資訊。

C選項的anti-mitochondrial antibody在排除其他鑑別診斷後，可作為primary biliary cirrhosis與Primary Sjögren’s syndrome共病的證據，也就是將膽道問題和唾腺變化視作兩個疾病，但無法解釋胰臟變化。D選項的Anti-smooth muscle antibodies為autoimmune hepatitis的血清證據，也無法解釋膽道與胰臟變化。

IgG4-related autoimmune disease好發於年紀較大的男性(>50歲)，可能影響多種器官，包括胰臟、肝臟、膽道(和Primary sclerosing cholangitis鑑別)、唾腺、淚腺、眼睛、甲狀腺、腎臟、血管、後腹腔(和Multicentric Castleman’s disease鑑別)、腸繫膜、顱內、性器官、肺部與皮膚等等，造成腺體/組織的纖維化、發炎、或形成腫塊等等。常見表現為type 1 autoimmunepancreatitis (70%合併IgG4 sclerosing cholangitis)與唾腺疾病(造成唾腺腫脹的Mikulicz disease與Sclerosing sialadenitis/Kuttner tumor)。診斷是透過血液內IgG4的數值(60-80%會上升，sensitivity85%、specificity 93% in one meta-analysis)與切片結果確立。切片的主要發現為淋巴漿細胞(lymphoplasmacytic)的大量浸潤合併>40% IgG4陽性細胞的存在(IgG4/IgG positive cell ratio
>40%)、席紋狀纖維化 (storiform pattern，指膠原纖維以放射狀方式排列) 、與閉塞性靜脈炎(obliterative phlebitis，指中型靜脈部分或全部堵塞，和primary sclerosing cholangitis的無發炎靜脈纖維堵塞不同)。順帶一提，針對autoimmune pancreatitis，日本在 2013 年有發表JapaneseConsensus Guidelines、Mayo Clinic也發表了HISORt criteria來協助診斷，有興趣的人可以再參考。


**故本題應選E。**

Ref.
1. Harrison’s Principles of Internal Medicine, 17th edition
2. Rheumatology Secrets, 3rd edition, 2015
3. [http://www.rheumatology.org/Portals/0/Files/ACR-EULAR-](http://www.rheumatology.org/Portals/0/Files/ACR-EULAR-) 2016 - Sjogrens-Classification-
Criteria.pdf
4. Dtsch Arztebl Int 2015; 112: 128– 35
5. 內科學誌 2016 ： 27 ： 19 - 28
6. Scientific Reports | 6:32035 | DOI: 10.1038/srep32035 (2016)
7. J Gastroenterol (2014) 49:567– 588

## Question 156

56 歲男性患者過去三年來時常有鼻竇炎及兩次流鼻血。最近發現腎功能有異常及咳血。胸部X光檢查發現肺野有數顆結節。血清學檢查發現：ESR及CRP增加，ANA 1:80 speckled，血液常規正常，proteinuria(++)。Urine RBC 10-15/HPF，WBC 7 - 9/HPF，cANCA 148 IU/mL (normal < 10 U/ml)。請問最有可能的診斷為何？

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- A. Polyarteritis nodosa
- B. Eosinophilia with polyangitis
- C. Sarcoidosis
- D. Granuomatosis with polyangitis
- E. Paragonimiasis

### Correct Answer: D

上呼吸道影響(鼻竇炎+流鼻血)、腎臟功能異常(腎功能異常、蛋白尿、血尿/膿尿)與下呼吸道影響(咳血、肺部結節)的表現皆指向ANCA vasculitis。C-ANCA陽性者，Granuomatosis withpolyangitis的機會最大。

(A) Polyarteritis nodosa(PAN)為中小血管的血管炎，主要影響周邊神經(mononeuritis multiplex)、
皮膚(palpable purpura、ulcers、livedo、nodules)、腹腔(因腸系膜血管炎而造成的腹痛與肝功能
異常)、肌肉與腎臟(renal artery aneurysm and infraction→高血壓)的血管，鮮有肺部(基本上不
會)、與ENT field表現，且ANCA應為陰性。值得一提的是，PAN和B肝感染有關，在初感染
的前六個月最容易發生，且較容易有睪丸炎(orchitis)、高血壓、與腎臟梗塞的表現。

(B) Eosinophilia with polyangitis的臨床表現跟Granuomatosis with polyangitis接近，但多數為P-
ANCA陽性。

(C) Sarcoidosis比較少影響腎臟，且ANCA應為陰性。
(E) Paragonimiasis衛式肺吸蟲病。幼蟲在被吞下後，可以穿行過腹腔而穿入肺臟形成結節，進而造成咳血。經過各個器官時會造成器官的損傷。蟲體移行時會有eosinophilia的現象。題幹中無相關病史和進一步描述。


(圖片來自wiki，改自美國CDC)

故選D。

Ref.
1. Rheumatology Secrets, 3rd edition, 2015
2. https://zh.wikipedia.org/wiki/File:%E8%A1%9B%E6%B0%8F%E8%82%BA%E5%90%B8%E8%9F%B2%E7%94%9F%E6%B4%BB%E5%8F%B2.gif

## Question 157

下列有關病因與關節炎屬性的配對中，何者最為正確？

---
- A. Staphylococcus aureus – chronic monoarticular arthritis
- B. Reactive arthritis – acute monoarticular arthritis
- C. Rheumatoic arthritis – chronic polyarticular arthritis
- D. Mycobacterium tuberculosis – acute polyarticular arthritis
- E. Neisseria gonorrhoeae – acute monoarticular arthritis

### Correct Answer: C

(A) Staphylococcus aureus造成的septic arthritis以急性單關節炎為主要表現。(X)
(B) Reactive arthritis的表現以非對稱的寡關節炎(asymmetric oligoarthritis)為主，且主要影響下肢
的大關節。(X)
(C) Rheumatoic arthritis以慢性多關節炎為主要表現，主要影響小關節。(O)
(D) TB造成的骨骼關節感染以脊椎為最多(Pott disease)，約占50%，通常以單脊椎為主要表現，但發現時常已經影響到椎間盤與鄰近的脊椎而形成cold abscess。30%的病患是以周邊關節感染為表現，一般以負重的大關節為主(股關節、膝關節與踝關節)，且多是單關節的慢性感染(slow-onset chronic monoarthritis)。(X)
(E) Neisseria gonorrhoeae造成的關節炎分成菌血階段(bacteremic stage)與化膿階段(suppurative
stage)。在症狀開始的前 48 到 72 小時屬於菌血階段，症狀以會移動的多關節疼痛與發炎(migratory polyarthralgia)為主(70%)，同時可能有發燒、tenosynovitis與皮膚炎(斑丘疹與小水泡最為常見)的表現，monoarthritis只佔 3 成。此時關節液的培養結果多為陰性。在 72 小時後進入化膿階段，約有50%的病人會發展成septic arthritis，此時血液培養轉為陰性，但關節液培養結果可能轉為陽性。影響關節以膝蓋為最多，但手腕、腳踝、手肘、或手的小關節也常受到影響。(X)

Ref. Rheumatology Secrets, 3rd edition, 2015

## Question 158

下列有關RA患者的關節外表現(extra-articular manifestations)的組合中，何者最為正確？

1. Keratoconjunctivitis sicca
2. Pleural effusion
3. Thromboembolism
4. Oral ulceration
5. Panniculitis
6. Ascites
7. Erythema nodosum
8. Uveitis
9. Interstitial lung disease
10. IgA nephropathy

---

- A. (1)+(3)+(5)
- B. (1)+(2)+(9)
- C. (3)+(4)+(5)
- D. (2)+(7)+(8)
- E. (5)+(9)+(10)

### Correct Answer: B

(1) Keratoconjunctivitis sicca：RA可以造成secondary Sjögren’s syndrome(O)
(2) Pleural effusion：RA可以造成pleural effusion(O)
(3) Thromboembolism：有世代研究顯示RA病患得到DVT和肺栓塞的風險較高。(O)
(4) Oral ulceration：RA較少oral ulcer的報告，反而是使用MTX會有此副作用。(X)
(5) Panniculitis：在RA罕見，但有案例報告。(O)
(6) Ascites：在RA少見，但有案例報告。(O)
(7) Erythema nodosum：RA的皮膚症狀以subcutaneous nodules、pyoderma gangrenosum、vasculitic rashes、leg ulceration、amyloidosis為主。Erythema nodosum的成因除了感染外，在風濕科應考慮sarcoidosis、inflammatory bowel disease、Behçet's disease。(X)
(8) Uveitis：RA較常造成scleritis與episcleritis(X)
(9) Interstitial lung disease：RA可以造成ILD(O)
(10) IgA nephropathy：RA較少造成腎臟的影響，比較常發現的表現是membranous nephropathy、vasculitis與secondary amyloidosis。有個案報告等級的文章提到有IgA nephropathy的表現。(O)

統合以上，教科書中提及比較常見的症狀包括了(1)、(2)、(9)，(3)有世代研究支持，而(5)、(6)、(10)有案例報告。若以常見程度來選擇，B較為合適。

Ref.
1. Rheumatology Secrets, 3rd edition, 2015
2. EULAR Textbook on Rheumatic Diseases, 2015
3. Clin Exp Rheumatol. 2016 Jan-Feb;34(1):126-8. Epub 2016 Jan 8.
4. Ann Rheum Dis. 2014 Oct;73(10):1774- 80
5. BMJ Case Reports 2015; doi:10.1136/bcr- 2014 - 207142
6. Reumatizam. 2009;56(1):30-5.

## Question 159

下列有關anti-phospholipid antibody syndrome的敘述中，何種組合最為正確？
1. Bleeding tendency
2. aPTT prolongation
3. PT shortening
4. 會引起deep vein thrombosis
5. 與SLE recurrent abortion有相關
6. 常常會引發cutaneous vasculitis
7. 對glucocorticoids的治療有效
8. 與SLE患者VDRL (venereal disease research laboratory) false positive有關
9. 與SLE患者的leukopenia有關

---

- A. (1)+(3)+(6)
- B. (2)+(4)+(8)
- C. (5)+(7)+(9)
- D. (2)+(8)+(9)
- E. (4)+(5)+(6)

### Correct Answer: B

(1) Bleeding tendency：APS以容易造成栓塞而非出血表現(X)
(2) aPTT prolongation：超過一半有lupus anticoagulant的病患同時會有aPTT延長的狀況，但aPTT正常的病人無法排除lupus anticoagulant的存在(O)
(3) PT shortening：在一般狀況下(不考慮肝臟問題、維他命K缺乏、或者使用warfarin)，有APS的病患並不會出現PT延長的情況，除非病患的lupus anticoagulant的濃度非常高。若排除以上狀況，且lupus anticoagulant的濃度也不高，就要小心是否有factor II(prothrombin)deficiency的問題。如果病患有factor II deficiency，病患可能反而會傾向出血而非形成血栓，因而在使用抗凝血藥物時的出血風險會大為提高。此外病患基本上不會出現PT縮短的狀況(X)
(4) 會引起deep vein thrombosis：血管栓塞為APS的臨床定義之(O)
(5) 與SLE recurrent abortion有相關：流產為APS的臨床定義之一(O)
(6) 常常會引發cutaneous vasculitis：APS最常見的皮膚表現為livedo reticularis，而livedo reticularis不一定由vasculitis造成(X)
(7) 對glucocorticoids的治療有效：Primary APS的治療以anti-coagulation為主，如果有arterial thrombosis可以考慮加上aspirin。Steroid的角色目前未定，多數的文獻僅在catastrophic APS使用脈衝與高劑量類固醇。(X)
(8) 與SLE患者VDRL (venereal disease research laboratory) false positive有關：Anticardiolipin陽性的病患，可能有高達50%的病患會有VDRL偽陽性的狀況。(O)
(9)與SLE患者的leukopenia有關：APS和thrombocytopenia與AIHA比較有關。(X)

正確的選項有(2)(4)(5)(8)

Ref.
1. Rheumatology Secrets, 3rd edition, 2015
2. Autoimmunity Reviews 14 (2015) 401– 414

## Question 160

一位病人被發現有紅血球過多症，下列變化在原發性多血症病患較次發性多血症病患為常見，何者例外？

---

- A. Leukocytosis
- B. Thrombocytosis
- C. Basophilia
- D. High erythropoietin level
- E. Splenomegaly

### Correct Answer: D

A.B: PV的Definition為↑ in RBC mass ± ↑ granulocytes and platelets in the absence of
physiologic stimulus (小麻5th: polycythemia vera)

C: The most common causes of basophilia include the following:
- Any of the classic myeloproliferative neoplasms (ie, chronic myeloid leukemia, primary myelofibrosis, polycythemia vera, essential thrombocytosis)
- Other hematologic malignancies (eg, basophilic leukemia, mastocytosis, hypereosinophilic syndrome, atypical acute and chronic leukemias, myelodysplastic syndrome)
- Allergic or inflammatory reactions, including hypersensitivity reactions, ulcerative colitis, rheumatoid arthritis
- Endocrinopathy, including hypothyroidism (myxedema), administration of estrogens
- Infections, including viral infections, tuberculosis, helminth infections (Uptodate: Approach to the patient with neutrophilia)

D: if Epo ↓, PV likely (小麻: polycythemia vera)，所以EPO上升應該是造成次發性多血症的原因

E: Signs: plethora, splenomegaly, hypertension, engorged retinal veins (小麻: polycythemia vera)

## Question 161

一位 63 歲男性在健檢時被發現白血球數目增高，其血液抹片如圖所示。這些細胞表現CD5/CD19/CD20/CD23，但CD2/CD3/CD10為陰性。這位病人最可能的診斷為？


- A. Chronic myeloid leukemia
- B. B cell chronic lymphocytic leukemia
- C. Follicular lymphoma
- D. Mantle cell lymphoma
- E. Adult T cell lymphoma/leukemia

### Correct Answer: B

1. Pathway of normal B cell differentiation and relationship to B cell lymphomas: HLA-DR,
CD10, CD19, CD20, CD21, CD22, CD5, and CD38
2. Pathway of normal T cell differentiation and relationship to T cell lymphomas: CD1, CD2, CD3, CD4, CD5, CD6, CD7, CD8, CD38, and CD71 ( Harrison 18ed: Chapter 110. Malignancies of Lymphoid Cells)
3. 所以是B cell 系列的 (A和E就可以排除)
4. 在血液抹片中可以看到好幾顆的blast cell所以答案應該就是B cell chronic lymphocytic leukemia
5. 另外Mantle cell lymphoma 比較不會有CD23
6. Follicular lymphoma 比較不會有CD5



http://www.nhlcyberfamily.org/tests/cdmarkers.htm

## Question 162

下列藥物與其作用機轉的配對，何者有誤？

---

- A. Bortezomib : proteosome inhibitor
- B. Imatinib : tyrosine kinase inhibitor
- C. Ruxolitinib : JAK inhibitor
- D. Azacitidine : demethylation agent
- E. Ibrutinib : anti-CD30 antibody

### Correct Answer: E

E: Ibrutinib is a Bruton's tyrosine kinase (BTK) inhibitor (Micromedex: Ibrutinib)
- Ibrutinib (Imbruvica) is a small molecule drug that binds permanently to a protein, Bruton's tyrosine kinase (BTK), that is important in B cells; the drug is used to treat B cell cancers like mantle cell lymphoma, chronic lymphocytic leukemia, and Waldenström's macroglobulinemia, a form of non-Hodgkin's lymphoma.

## Question 163

一位病人主訴呼吸急促，血液檢查顯示Hb 9.6 gm/dL，白血球及血小板數目正常，血液抹片如圖所示。此病人最可能的診斷為？



---

- A. Aplastic anemia
- B. Iron deficiency anemia
- C. Hemolytic anemia
- D. Vit B12 deficiency anemia
- E. Thalassemia

### Correct Answer: C

A. Aplastic anemia：除了pancytopenia外Reticulocyte比例會降低，主要還是以bone marrow來診斷，而非peripheral smear
B. Hypochromic, microcytic anemia due to iron-deficiency.（如圖表 1）


C. Blood smear of Hemolytic anemia :
1) polychromasia :這張抹片可以看到polychromasia，就是reticulocyte 跑到周邊來,這些reticulocyte呈藍染，在anemia到一定程度時就可以看到，或是cancer withbone marrow infiltration時也可以看到
2) 圖中可以看到一些spherocyte，autoimmune hemolytic anemia或hereditary spherocytosis 都可以出現這種表現

D. Vit B12 deficiency : hypersegmented neutrophil,ovale macrocytes, anisocytosis , 甚至嚴重時也會出現poikilocytosis （圖表 2）


E. thalassemia 也是hypochromic, 有時可以看到targeted cell （圖表 3）


## Question 164

下列有關heparin引發血小板低下症的敘述何者有誤？

---

- A. 第一次使用的病人，一般在使用後 2 至 3 星期發生
- B. Low-molecular-weight heparin發生機會較unfractionated heparin小
- C. 容易併發栓塞
- D. 血小板很少掉到20000/uL以下
- E. 病人血中可偵測到抗heparin/platelet factor 4的抗體

### Correct Answer: A

1. 一般第一次使用約在 5 - 7 天左右發生，若在 90 天內re-exposure時有可能abrupt發生。單純一個dose就有可能誘發HIT的產生，major surgery後也可能發生。Heparin的發生率是LMWH 的十倍左右。Complication跟一般的thrombocytopenia不一樣，容易發生靜脈栓塞的情形 (DVT/PE)，動脈栓塞 (peripheral artery或stroke)也都有可能，thrombosis risk會持續約三周。是透過autoantibody (anti-platelet factor 4 –heparin)為機轉，這種抗體被誘發後約在身體裡面存在50~90天，消失後若再度產生需要約 5 天的時間。診斷上若PLT decrease >50% + heparin use in the past one week，通常在1~3天降 到nadir 約40000~80000/uL 左右, 很少會更低


2. Anti–PF4–heparin enzyme immunoassays :如果negative幾乎可以排除HIT, negative PPV 98%,但positive的病人中有產生thrombosis的機率只有2~15%
3. Treatment for HIT: direct thrombin inhibitor : argatroban , anti-Xa :danaparoid
4. Avoid vitamin K, prophylatic PLT transfusion! (不能輸platelet)

Ref : N Engl J Med 2015;373:252- 61

## Question 165

大部分骨髓增生不良症候群(Myelodysplastic syndrome, MDS)的病人都被發現有基因突變。其中refractory anemia with ring sideroblasts與那一種突變特別有關？

---

- A. KIT
- B. JAK2
- C. SFS3B1
- D. DNMT3A
- E. MYC

### Correct Answer: C

1. SF3B1 : MDS with > 1% ring sideroblast 的病人中有些人帶有SF3B1 mutation，並且預後比wt的人好~
2. KIT mutation is associated with mastocytosis
3. JAK2 跟MPN相關
4. DNMT3A 在 2010 年才被identified，是一個coding DNA methyltransferase的gene，~20% AML/MDS的病人有此gene mutation，其他各種hematological malignancy也都有一定比例有此gene的變化，常被視為一個pre-leukemic lesion (Nature Reviews Cancer 2015; 15: 152–165)
5. MYC的變化跟很多myeloid, lymphoid 的neoplasm都有關係

## Question 166

急性前骨髓芽細胞白血病(Acute promyelocytic leukemia, APL)在治療後可以用何種生物標追蹤其微量殘存疾病(minimal residual disease)

---

- A. NPM1 mutant
- B. BCR-ABL
- C. RUNX1-RUNX1T1
- D. PML-RARA
- E. CBFB-MYH11

### Correct Answer: D

1. MRD意指白血病經過化療後達complete remission時，骨髓中仍殘存著微量癌細胞，靠傳統bone marrow smear看不到，必須用流式細胞儀來偵測骨髓中微量殘存癌細胞。 MRD可以預測病人疾病復發的可能性，也可以用來看治療的反應。
2. APL特色是會有 t(15;17)/PML-RARA，所以可用來當MRD的marker
3. AML可以用t(8;21)/AML1-ETO(RUNX1-RUNX1T1)、inv(16)/CBFB-MYH11、NPM1 mutation、DNMT3A、IDH1/2、CEBPA等當MRD的marker。 FLT3/ITD因為是不穩定的基因變異，所以比較不能用來追蹤AML。
4. t(9;22)/BCR-ABL最主要會出現在CML，不過如果出現在ALL或AML也可以用來當MRD的marker。
5. 下圖是acute leukemia (包含AML和ALL)的Cytogenetics變化


Graph from Dr.侯信安，data from Blood Rev 2004;18(2):115- 36

## Question 167

一位 55 歲病人最近一星期出現兩腳多處瘀青，其他無特殊異常。軟組織超音波檢查顯示有血腫。抽血檢查發現PT為 12 秒(參考值9.8~11.5)，INR 0.95，PTT 58秒(參考值25.6~32.6)。mixing test顯示， 0 小時PTT為 37 秒， 2 小時為 54 秒。這位病人最可能的診斷為：

---

- A. Acquired hemophilia
- B. Antiphospholipid syndrome
- C. von Willebrand disease
- D. Factor XII deficiency
- E. Disseminated intravascular coagulation

### Correct Answer: A

1. 本題考mixing study以及PT/aPTT。血中的coagulator factor只要有約50%就可讓PT/aPTT正常，所以如果混和後如果可以矯正就偏向factor deficiency，如果不行就偏向factor inhibitor，不過就算是有inhibitor存在，mixing的結果還是會有部分correction。
2. 到底矯正多少叫做有矯正，參考下圖。舉例第一列mixing後的值 – PT/aPTT的上限值差< 4秒，則可以88%正確診斷deficiency，但有100%正確診斷inhibitor。本題中矯正後0h和上限值差4.4秒，仍偏向inhibitor，但deficiency可能性還是有的 (Sn 88%, Sp 100%)！ (Semin Thromb Hemost 2013 ;39:283–290)


3. 首先考慮原始的PT/aPTT，可以看到只有aPTT延長。可刪去E。 (Ref: 蔡偉老師上課講義)


4. 考慮mixing test的結果。因為0h的結果仍有延長而且2h的結果變更長，所以表示不是deficiency，排除C、D。比較0h和2h的結果可以發現mixing aPTT又變長了，這是factor VIII inhibitor的特色，所以答案是A。如果是lupus anticoagulant則一開始就會很長。

5. acquired hemophilia A = autoantibody against factor VIII。這種inhibitor的特色是slow acting kinetics，而且是temperature dependent，當mixing test在 37 °C放 1 - 2 小時候，其活性最大，可以看到mix aPTT比一開始還要長，有意義的延長是 10 秒以上，有些例子甚至剛混和時的mix aPTT會是正常的。 (Semin Thromb Hemost 2013;39:283–290)。

## Question 168

一位 45 歲病人因胃痛就診，胃鏡檢查顯示有 2 公分大腫瘤，切片及病理檢查證實為marginal zone B-cell lymphoma, H. pylori陽性；分期檢查未發現其他地方有被侵犯。對此病人最適當的治療為何？

---

- A. Surgery
- B. Anti-H. pylori treatment
- C. Rituximab
- D. Rituximab plus oral chemotherapeutic drug
- E. Rituximab plus CHOP(Cyclophosphamide, Adriamycin, Vincristine and Prednisolone)

### Correct Answer: B

1. 本題考gastric MALToma早期，且H. pylori陽性
2. marginal zone B-cell lymphoma (MZL) 是indolent的lymphoma，依照出現的部位可以分為三型：nodal、extranodal、splenic。而extranodal marginal zone lymphoma又叫做low grade B cell lymphoma of mucosa-associated lymphoid tissue (MALT)，包含gastric MALT以及non-gastric MALT。
3. Nodal MZL：預後較差，若需治療以化療為主
4. Splenic MZL：只有脾大，少淋巴結，有時會帶splenic lymphoma with villous lymphocyte(SLVL)，治療以切脾為主
5. Gastric MALToma大約占gastric lymphoma的40%，另外60%是DLBCL為主，剩下是很多罕見的lymphoma (World J Gastroenterol 2014; 20(11): 2751–2759)。
6. 目前認為gastric MALToma和H. pylori造成的chronic gastritis有關，在切片下約 92-98.3%的gastric MALToma可以找到H. pylori，不過在感染H. pylori的病人只有0.66%會發生gastric MALToma (Gut 2002;50(Suppl III):iii19–iii24)。
7. gastric MALToma可以發現有t (11; 18) (q21; q21)、t (14; 18) (q32; q21)、t (1; 14) (p22;q32)、t (3; 14) (p14.1; q32)四種translocation，以t (11; 18)最常見。如果有這四種translocation，則MALToma對H. pylori eradication治療無反應。
8. 治療：重點在期別以及H. pylori的有無
a、 早期 (Stage I/II) & H. pylori陽性：治療H. pylori。約有 50 - 83%可達到complete remission，在追蹤6.8年後只有22% relapse。
b、 早期但H. pylori陰性、對H. pylori eradication治療後療效不佳、有t(11;18)(q21;q21)：給予local R/T或手術(少用)
c、 晚期 (stage III/IV)：如果H. pylori陽性還是可以殺看看。不過會等到疾病產生症狀再治療，一般是給rituximab +/- chemotherapy。


World J Gastroenterol 2014; 20(11): 2751– 2759
Ref: UpToDate: Management of gastrointestinal lymphomas、Treatment of marginal zone (MALT)
lymphoma、劉家豪老師上課ppt

## Question 169

下列何者為Tumor lysis常見的變化？(應選出所有正確答案)
1. Hyperuricemia 2. Hyperkalemia 3. Hypercalcemia 4. Renal failure

---

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

### Correct Answer: D

1. 常見↑K、↑uric acid、↑P、↓Ca、metabolic acidosis
2. 會有renal failure (因urate nephropathy)
Ref: 小麻

## Question 170

一 55 歲男性病人診斷有惡性黑色素細胞瘤(melanoma)合併肺臟與骨骼轉移，目前一般體能狀況良好。他的腫瘤基因檢測證實BRAF V600E突變陽性。建議此病人接受何種治療可以有最佳的腫瘤緩解率(response rates)?

---

- A. Cisplatin
- B. Dacarbazine
- C. Vemurafenib
- D. Interleukin- 2
- E. Hospice care

### Correct Answer: C

1. Vemurafenib and dabrafenib, inhibitors of BRAF, have demonstrated dramatic antitumor activity in phase III trials in patients with advanced disease whose tumors have characteristic mutations in BRAF. (uptodate: Molecularly targeted therapy for metastatic melanoma)
2. Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation (N Engl J Med 2011; 364:2507-2516): At 6 months, overall survival was 84% (95% confidence interval [CI], 78 to 89) in the vemurafenib group and 64% (95% CI, 56 to 73) in the dacarbazine group.

## Question 171

一 65 歲男性，從 16 歲開始抽菸，到目前仍平均一天約抽 1 包香菸。他在最近一次健康檢查中，CT掃描發現左下肺葉外圍(periphery)有單一個10mm直徑大小的肺結節(nodule)，並沒有發現明顯的縱膈腔淋巴結腫大，他在 2 年前有檢查過CXR，並沒有發現這一個結節。目前他並無任何顯著的呼吸系統症狀，肺功能檢查FEV1為87% predicted，FVC為91% predicted，diffusion capacity為81% predicted。建議下列下一步處置何者最為適當?

---

- A. 進行FDG-PET-CT正子斷層掃描攝影檢查
- B. 進行Bronchoscope with biopsy以確診
- C. 3 個月後進行Chest MRI掃描以評估interval growth
- D. 轉介胸腔外科進行Video-assisted thoracoscopic (VATS) biopsy，若證實為惡性，則合併病灶切除
- E. 轉介放射腫瘤科進行Stereotactic radiation

### Correct Answer: D

首先看到image上有lession，在uptodate (Diagnostic evaluation and management of the solitary
pulmonary nodule) 上先分Patients with adequate prior imaging or Patients without adequate prior imaging，這一題先前有照過X ray，所以走Patients with adequate prior imaging，再分成 Growing nodule or Stable nodule

- Growing nodule — A solid or subsolid nodule that has clearly grown on serial imaging tests has a high likelihood of being malignant and should be evaluated pathologically with excision or biopsy.
- Stable nodule — Experts agree that the vast majority of solid SPNs that are unchanged on serial CT scan over a two-year period and subsolid SPNs unchanged over a three-year period are likely benign and do not need further diagnostic evaluation. Occasionally, patients in this category may require extended periods of CT surveillance to ensure stability, especially if low grade adenocarcinoma or carcinoid is suspected. (uptodate: Diagnostic evaluation and management of the solitary pulmonary nodule)
-
這位病人他在 2 年前有檢查過CXR，並沒有發現這一個結節，現在有一個10mm直徑大小的肺結節(nodule)應該算是Growing nodule，所以應該建議should be evaluated pathologicallywith excision or biopsy，所以答案是D

Uptodate 流程圖:


A:如果病人沒有先前的影像，他又落在intermediate risk or low risk (Brock University cancer prediction equation)，就可以選A，但是他有先前X ray
B:在左下肺葉外圍(periphery)所以做Bronchoscope with biopsy有困難
C:這個病人走流程圖，除非是沒有先前的影像，又是low risk才會或是nodule小於8mm
E病人stage 最可能是1a，如果真的是malignancy應該也是開刀，而不是轉介放射腫瘤科進行Stereotactic radiation

## Question 172

一位 66 歲男性因突然發覺右側眼瞼下垂與視力模糊而到急診就醫，病人主訴過去都沒有類似的症狀發生，只是過去約 3 個月以來，他自覺右肩與右上臂疼痛的問題，他的家庭醫師先診斷為發炎性疼痛(shoulder bursitis)並給予藥物，但疼痛並未能完全控制。他平均每天抽菸約一包，已有超過 30 年之久，長期有COPD與慢性咳痰的問題。急診理學檢查發現右眼瞼ptosis且兩側pupils大小不等，右側pupil 2 mm且not reactive，左側pupil 4 mm且reactive，兩眼球的各
眼外肌活動的各方向均正常(full and free)。肺部聽診大致正常。肢體檢查發現右手掌的intrinsic 肌肉已有wasting現象。 你推測他最可能的臨床診斷為何?

---

- A. CXR可見到一cervical rib的存在
- B. Eaton-Lambert myasthenic syndrome (Eaton-Lambert重症肌無力症候群)
- C. 小細胞肺癌(Small cell lung cancer)已有midbrain轉移
- D. CXR可見到右上肺尖(apical)肋膜增厚且合併有一個約 2 公分厚度的腫塊陰影
- E. 縱膈腔淋巴結腫大，壓迫上腔靜脈(SVC)，造成SVC症候群

### Correct Answer: D

1. cervical rib的症狀有Pain is mild or absent. Weakness and wasting of intrinsic muscles of the hand and diminished sensation on the palmar aspect of the fifth digit(Harrison 18ed.)，但是病人有眼瞼ptosis和pupil的問題，所以不像。
2. Eaton-Lambert myasthenic syndrome: Most patients present with complaints of slowly progressive proximal muscle weakness. Symmetrical muscle involvement is the rule. (uptodate: Clinical features and diagnosis of Lambert-Eaton myasthenic syndrome)，這個病人是單側比較不像。
3. midbrain轉移:中腦受傷可能傷到第三腦神經應該是受傷側pupil dilation，這個病人是縮小
4. 右眼瞼ptosis，右側pupil 2 mm且not reactive，左側pupil 4 mm且reactivHorner syndrome。再加上右手掌的intrinsic肌肉已有wasting現象 Pancoast tumors。
5. Pancoast tumors typically present as an insidious onset of pain in the upper arm, sensory disturbance in the medial aspect of the forearm and hand, and weakness and atrophy of the intrinsic hand muscles along with an ipsilateral Horner syndrome. (Harrison 18ed.)
6. SVC syndrome: Dyspnea is the most common symptom. In addition, patients frequently complain of facial swelling or head fullness, which may be exacerbated by bending forward or lying down. Other symptoms include arm swelling, cough, chest pain, or dysphagia. Patientswith cerebral edema may have headaches, confusion, or possibly coma. (uptodate: Malignancy-related superior vena cava syndrome) 這個病人都沒有這些症狀。

## Question 173

一 33 歲女性因右側乳房腫塊來就醫。約一週前她在淋浴時發現這一腫塊，並沒有nipple的異常分泌物，也沒有任何紅腫或不適，她過去也沒有特定醫療病史。理學檢查觸診發現右側乳房的「右上外側四分之一」部位有一個約1.5 x 2.0公分的腫塊，左側乳房正常，兩側腋下淋巴 結均無腫大。 4 週後再次理學檢查依然一樣。於是進行細針抽吸術，抽出約2.5毫升清澈的液 體，之後腫塊就觸診不到了。下列建議何者最為適宜?

---

- A. 立即進行Mammography進一步評估
- B. 立即進行Breast MRI偵測與分辨殘餘液體的分布
- C. 立即轉介Breast surgeon進行切除手術
- D. 日後此病人不應餵她的小孩母乳
- E. 安排此病人 1 個月後再回診追蹤，以決定後續的檢查或治療需要與否

### Correct Answer: E

D/D of a breast mass : benign  fibroadenoma, fibrocystic change, cyst, galactocele, fat necrosis 診斷breast mass的一線工具是mammography 和ultrasound
ACR BI-RADS mammography assessment category 可以幫助臨床決策



本題解：原則上PE摸到mass在資源可得的情況下，會進行至少一種影像學檢查，如果PE可以感受到是cystic lesion，用超音波檢查較合適，也可以決定後續處理。一般如果是simplecyst，malignant risk < 10%，可以不進行抽吸，若進行aspiration後液體為澄清狀，cytology多半也呈negative。本題題幹並非最標準處理，若要aspiration前，先進行ultrasound檢查，若有solid part 或complex cyst進行biopsy會較恰當。

## Question 174

一個身體狀況大致正常的 65 歲女性進行健康檢查，colonoscope在升結腸部位發現 2 個大小分別為1.2公分、1.4公分的扁平樣sessile (flat-based)息肉，內視鏡檢同時進行內視鏡息肉切除，病理報告均為絨毛樣腺瘤(villous adenoma)，並無結腸癌。以下建議何種最適當?

---

- A. Abdominal and Pelvic CT scan
- B. Partial colectomy
- C. Reassurance only
- D. Follow-up colonoscopy in 3 years
- E. Follow-up colonoscopy in 10 years

### Correct Answer: D

此題考colon cancer screening for average risk group

Increased risk :
- A personal history of colorectal cancer or adenomatous polyps
- A personal history of inflammatory bowel disease (ulcerative colitis or Crohn’s disease)
- A strong family history of colorectal cancer or polyps
- A known family history of a hereditary colorectal cancer syndrome such as familial adenomatous polyposis (FAP) or Lynch syndrome (hereditary non-polyposis colon cancer or HNPCC)



Ref: Guidelines for colonoscopy surveillance after screening and polypectomy: A consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012; 143:844.

## Question 175

低劑量胸腔CT掃描發現單一肺結節(solitary pulmonary nodule)，下列何者為真?

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- A. About 70% of incidentally found pulmonary nodules are benign.
- B. A lobulated and irregular contour is more indicative of malignancy than a smooth one.
- C. Ground-glass nodules should be benign.
- D. Multiple nodules indicate malignant disease.
- E. Absence of growth over a period of 6 - 12 months is sufficient to determine whether it is benign.

### Correct Answer: B

1. 定義solitary pulmonary nodule: round lesion, < 3 cm, completely surrounded by pulmonary
parenchyma, without other abnormalities
2. The incidence of malignancy 10 ~ 70 %, dependent on age, smoking and other risk factor
3. 型態上favor malignancy: Corona radiata (very fine linear strands extending 4 to 5 mm
outward from the nodule, speculated appearance), scalloped border, larger size
4. 型態上favor benign : Calcification within a nodule (laminated or central pattern 
granuloma, “popcorn” pattern + fat + cartilage hamartoma, stippled or
eccentriccancer) ，non-upper lobe/ GGO 並不是區分benign 或是malignant的hint。
Growth rate : volume-doubling time for malignant bronchogenic tumors通常在 1 month ~ 1 year間, 通常用 ”HRCT” 追蹤兩年都沒有變化可以視為benign，但是bronchoalveolar- cell carcinomas和 typical carcinoids有時長大的更慢。
5. multiple small nodules f/u based on the largest one

Ref: ACCP 2013 guideline for lung cancer

## Question 176

一 55 歲男性接受健康檢查，肛門指檢(digital rectal examination，DRE)發現明顯的攝護腺腫大，且觸診已發現攝護腺右葉明顯結節，他已不記得前一次的DRE時間，也從未抽血測過攝護腺特異性抗原(prostate-specific antigen，PSA)數值。根據健康檢查的結果與臨床指引，建議下一步最適宜的處置為何?

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- A. 只測量一次PSA即可
- B. 現在與 6 個月後各測量一次PSA, 以計算PSA velocity
- C. 安排全身性骨骼同位素掃描以評估可能的轉移
- D. 安排在「經直腸超音波檢查」的導引下，進行攝護腺切片檢查
- E. 等 3 個月後再重複一次DRE檢查

### Correct Answer: D

1. PSA play the role of prostate cancer screening
- Fractionate PSA (free PSA/ total PSA): > 30% more benign, < 10% more malignant
- PSA velocity: when PSA 2.5~4 ng/mL  a change > 0.35 ng/mL/ y When PSA > 4 ng/mL  a change > 0.75 ng/mL/y  prompt a biopsy
2. DRE : ~ 20% of prostatic cancer cases were detected by DRE. All men with significant asymmetry, induration, or palpable nodularity of the prostate gland require “Biopsy”, particularly if > 45 y/o or have other risk factors for the disease
3. Bone scan only plays a role for detection of metastasis after malignancy is diagnosed.

Ref: uptodate

## Question 177

一 80 歲男性轉移性攝護腺癌病人，因意識狀態改變(altered mental status)而被家人送至急診。他因攝護腺癌定時接受goserelin肌肉注射抗荷爾蒙治療。急診理學檢查發現，血壓106/52mmHg，脈搏112/min，看來十分疲倦嗜睡且對胸骨壓痛反應極微弱，眼窩凹陷且黏膜乾燥，gag reflex仍intact，四肢對劇痛刺激的withdrawal均仍對稱，且rectal tone仍正常。異常實驗室數據creatinine 4.2 mg/dL，calcium 3.25 mmol/L (13.0 mg/dL)，albumin 2.6 g/dL。下列合適的處置，何者為非?

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- A. Dexamethasone
- B. Normal saline
- C. 當病人恢復euvolemic狀態時，給予Furosemide
- D. Calcitonin
- E. Palmidronate

### Correct Answer: A

1. 本題考prostate cancer造成之hypercalcemia的處置。病人有hypercalcemic crisis，併polyuria、dehydration、AMS、AKI (dehydration related)。
2. Correct Ca = 3.25 + (4-2.6) * 0.2 = 3.53 mmol/L (14.12 mg/dL)
3. 處置有


Ref: 小麻、UpToDate: Treatment of hypercalcemia

## Question 178

有些癌症病人雖然已經是轉移性的癌症期別(metastatic disease)，以手術切除方式治療，仍有" 少數"病人有長期存活或甚至「治癒的可能性」(potentially curable)。 下列狀況何者為真? (應選出所有正確答案)
1. 一位 58 歲女性結腸癌病人手術治療後， 2 年後有 3 顆肝臟轉移的結腸癌，均位於肝臟左葉，轉介至外科進行left hepatic lobectomy手術切除
2. 一位 25 歲男性病人有左股骨(femur)惡性骨肉瘤(osteosarcoma)病史，如今發現右下肺葉有1.2公分大小轉移病灶，轉介至外科進行right lower lobectomy of lung手術切除
3. 一位 75 歲男性病人因攝護腺癌轉移至多處脊柱骨骼(vertebrae)，轉介至泌尿腫瘤科先進行orchiectomy手術切除

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- A. 1
- B. 1+2
- C. 2+3
- D. 1+2+3
- E. 以上皆非
-
### Correct Answer: D

這題應該都會選D吧！任何可能都有阿 @_@
目前有報導的癌症有：

1. colorectal cancer with liver mets：不管是復發後轉移或者是一開始就轉移都有人在做！(Surg Oncol 2007;16(1):71-83)
2. osteosarcoma with lung mets：在primary osteosarcoma已經治好的病人，發生在肺部可切除的復發，約有 30 - 40%的五年存活 (Cancer 2005;104(8):1721-5)
3. renal cell carcinoma：在RCC但只有solitary mets的病人，做primary nephrectomy + metastatic tumor resection追蹤 3 年可以有 26 months median survival (World J Surg Oncol 2005; 3: 48)。NEJM也建議做cytoreductive nephrectomy ± metastasectomy (N Engl J Med 2017; 376: 354)
4. pancreatic cancer：在pancreatic cancer合併liver metastasis，術後最長存活65.4個月 (HPB (Oxford) 2006; 8(2): 85 – 88)
5. breast cancer with liver mets：在乳癌病人併發可切除的肝轉移，且沒有其他地方轉移，切除肝臟轉移+打化療， 5 年存活率為22% (Surgery 2000;127(4):383-9)
6. 看起來不行的有lung、HCC、NPC，如果有同事搜尋到相關的case report歡迎更新！
7. 在prostate cancer做orchiectomy是Androgen-deprivation therapy的一種，可用來治療 stage IV prostate cancer(Ref: 小麻)，有研究比較吃GnRH agonist和orchiectomy發現後者的副作用比較少 (JAMA Oncol 2016;2(4):500-7)。

## Question 179

一位 52 歲女性第三期乳癌病人，注射包含doxorubicin為主的CAF輔助性化學治療處方，注射化療後第 8 天病人因高燒39.2°C來到急診，合併寒顫與頭痛。急診初步檢查白血球總數490/μL (分類10% neutrophils，20% monocytes，70% lymphocytes)，胸部X光(CXR)檢查，尿液檢查，與中心靜脈導管均沒有明顯感染的證據，已由周邊與中心靜脈抽血進行血液培養檢查。 你建議下一步如何處置最適宜?

---

- A. 給予廣效性抗生素ceftazidime、vancomycin與voriconazole
- B. 給予廣效性抗生素ceftazidime與vancomycin
- C. 下一個或往後的相同處方化學治療療程，可預防性給予G-CSF (granulocyte colony-stimulating factor)
- D. (A)+(C)
- E. (B)+(C)

### Correct Answer: E

1. 本題考febrile neutropenia的處置。病人ANC = 49 。CAF = cyclophosphamide, Adriamycin, 5 - FU
2. 第一線經驗性抗生素要使用anti-pseudomonas，包含ceftazidime, cefepime, Tienam, meropenem, Tazocin。如果有central IV catheter可以給予vancomycin, teicoplanin。至於 empirical antifungal therapy建議是在對傳統抗生素 3 - 7 天無效以後再考慮。
3. Secondary prophylaxis (i.e. G-CSF given for a course of chemotherapy following a course with FN) is indicated if dose reduction below threshold or delay of chemotherapy is not desirable (e.g. treatment with a curative intent).

Ref: Management of febrile neutropaenia: ESMO Clinical Practice Guidelines (Ann Oncol 2016
Sep;27(suppl 5):v111-v118)

## Question 180

60 歲男性因主動脈剝離住院，住院中發生四肢無力與失禁，神經學檢查顯示四肢肌力為 1分，四肢肌腱反射增加，蹠反射（plantar reflex）為向上，針刺感覺（pin prick sense）自胸部以下喪失，關節活動感覺（joint position sense）則正常，何種病變的可能性最高？

---

- A. 硬腦膜外膿瘍（epidural abscess）
- B. 硬腦膜下血腫（subdural hematoma）
- C. 前脊椎動脈症候群（anterior spinal artery syndrome）
- D. 急性橫貫性脊髓炎（acute transverse myelitis）
- E. 硬腦膜外血腫（epidural hematoma）

### Correct Answer: C

- 四肢無力合併DTR上升、Plantar reflex向上表示為Upper motor neuron出了問題，可定位為大腦或是脊髓的問題。胸部以下感覺異常可知道問題出在脊髓而非大腦。又本體感覺正常表示Posterior column medial lemniscus功能正常；刺痛感喪失表示Anterolateralspinothalamic tract出了問題，可推斷是anterior spinal cord artery支配區域缺血的可能性最大。
- Anterior spinal cord artery主要由Vertebral artery、Subclavian artery及Aorta的分支所供應。若此條血管缺血會造成Anterior spinal artery syndrome。常見表現；某段脊柱以下的無力、合併痛、熱感喪失：同時保有正常的本體感覺、震動覺。Anterior spinal cord artery也是最常見spinal cord infarction的原因。


Ref: Dunn’s topical diagnosis in neurology, 4’th edition, p441

## Question 181

20 歲男性，因睡眠問題看診，主訴有下列症狀，何者是診斷猝睡症（narcolepsy）最明確（specific）的症狀？

---

- A. 白天上課時很容易睡著
- B. 大笑時會全身無力
- C. 常一躺下就睡著了
- D. 白天精神常不佳
- E. 剛睡醒時有幻覺

### Correct Answer: B

- Narcolepsy分成兩個Type：type 1及 type 2。兩種類型的患者都會覺得白天想睡覺，區別在於Type 1的患者會合併一種很特別的症狀：Cataplexy (情緒激動或是大笑時會出現短暫的頭頸部、膝蓋肌肉無力，嚴重時會讓病人跌倒)。
- 診斷上，病人覺得白天疲倦想睡覺可以有很多原因，但Cataplexy幾乎只會在Narcolepsy type 1出現。

Ref: UpToDate, Clinical features and diagnosis of narcolepsy in adults

## Question 182

40 歲女性因大量流汗、發燒、意識不清被送至急診，檢查顯示脈搏每分鐘 120 下、肢體僵直(rigidity)、肌腱反射增加 (hyperreflexia)。病人有憂鬱症病史，在精神科門診看診用藥，最有可能是下列何診斷？

---

- A. 韋尼克氏腦病（Wernicke's encephalopathy）
- B. 病毒腦炎（viral encephalitis）
- C. 抗精神藥物惡性症候群（neuroleptic malignant syndrome）
- D. 鎮靜劑過量（tranquilizer overdose）
- E. 血清症候群（serotonin syndrome）

### Correct Answer: E

- 憂鬱症病史，故有可能在門診接受selective serotonin reuptake inhibitor (SSRI)、serotonin-norepinephrine reuptake inhibitor (SNRI)、tricyclic antidepressants (TCA)或是monoamineoxidase inhibitor (MAOI)的處方。這些藥大多有增加serotonin的用途
- Wernicke’s encephalopathy: 無酗酒、挨餓等相關病史
- Viral encephalitis: 無感冒前驅病史，且不該有大量流汗
- Neuroleptic malignant syndrome (NMS): 主要表現為發燒、意識改變、僵直、自主神經失調。原因主要跟dopamine transmission blocker有關，如Haloperidol, risperidone, Primperan, Novamin, Seroquel，或是dopamine agonist的突然停用。憂鬱症病人較少拿到相關藥物。比起SS較少冒汗與hyperreflexia，但較常出現橫紋肌溶解、肝腎功能等異常
- 鎮靜劑過量：不該有發燒、流汗等相關症狀
- Serotonin syndrome (SS): 主要表現為發燒、心跳快、DTR上升、躁動、瞳孔擴張、潮紅、冒汗。配合病人病史。最有可能是該選項

Ref: UpToDate, Serotonin syndrome (serotonin toxicity)

## Question 183

30 歲女性因雙下肢無力、麻木與失禁就醫，脊髓液檢查顯示無白血球，葡萄糖為 70mg/dL、全部蛋白為75 mg/dL、白蛋白為50 mg/dL、IgG為20 mg/dL，血清的白蛋白為3000 mg/dL、IgG為1000 mg/dL，則她的IgG index是多少？

---

- A. ≧1.20
- B. 1.00~1.19
- C. 0.80~0.99
- D. 0.60~0.79
- E. <0.60

### Correct Answer: A

- IgG index的算法: [(IgG CSF/AlbuminCSF)/(IgGserum/Albumin serum)] = 1.2
- Elevation of IgG levels in the cerebrospinal fluid (CSF) of patients with inflammatory diseases of the central nervous system (multiple sclerosis [MS], neurosyphilis, acute inflammatory polyradiculoneuropathy, subacute sclerosing panencephalitis) is due to local central nervous system (CNS) synthesis of IgG.

Ref: [http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8009](http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/8009)

## Question 184

55 歲男性，長期於某一工廠工作，近 6 個月有漸進的步履變小、動作變慢、平衡變差，診斷為巴金森氏症（parkinsonism），有 2 位工廠同事有類似但較輕的症狀，最需要懷疑為何種中毒？

---

- A. 鉛（lead）
- B. 錳（manganese）
- C. 汞（mercury）
- D. 砷（arsenic）
- E. 銅（copper）

### Correct Answer: B

- 同事有類似症狀暗示環境暴露導致疾病產生，選項中，金屬中毒以類似巴金森症狀表現的有：慢性錳、慢性汞中毒。但汞中毒會合併其它症狀如牙齦炎、視力受損。故此病人選錳中毒。
- 鉛中毒：腦病變、運動神經病變、抽搐、腹部絞痛、腎衰竭
- 錳中毒：認知情緒障礙、行走困難、僵硬、抖動、無法說話 (類似巴金森氏症)
- 汞中毒：噁心、嘔吐、口腔炎、皮膚疹、視力受損、肌肉萎縮、抖動 (類似巴金森氏症，但多了其他表現)
- 砷中毒：皮膚癌 (Boween’s disease)、貧血、中樞及周邊神經病變、烏腳病
- 銅中毒：可經由尿液、膽汁排出。短時間攝取大量才有症狀：肝炎、噁心、嘔吐、溶血、腎衰竭、抽搐等 (類似Thrombotic microangiopathy syndrome)

Ref: 林杰樑醫師, http://www.greencross.org.tw/toxin/heavy-metal/heavy_metal.htm

## Question 185

慢性腎臟疾病（chronic kidney disease）病人接受透析治療的時候，發生透析失衡症候群（dialysis disequilibrium syndrome），下列敘述何者為非？

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- A. 多在透析結束時發生，而非透析開始前發生
- B. 會表現突眼、眼壓高
- C. 會表現頭痛、癲癇
- D. 因水分自腦部脫出太多所致
- E. 因移除尿素太快所致
-
### Correct Answer: D

- Dialysis disequilibrium syndrome的主要表現：多發生在透析當中或透析剛結束，有人認為是因血中BUN移除太快，此時腦細胞內有相對較高的BUN，造成滲透壓差，使得水分進入腦細胞內，造成腦水腫。產生Headache, nausea, disorientation, restlessness, blurred vision,asterixis等症狀

Ref: UpToDate, Dialysis disequilibrium syndrome

## Question 186

25 歲男性 1 年前曾發生車禍致鎖骨骨折，半年前起漸進右上肢無力、麻木與冰冷就診，神經學檢查顯示右上肢內側感覺遲鈍、右手肌力較差，右臂血壓為90/60 mmHg、左臂血壓為130/80 mmHg，最可能診斷為何？

---

- A. 頸神經根病變（cervical radiculopathy）
- B. 胸廓出口症候群（thoracic outlet syndrome)
- C. 臂神經叢病變（brachial plexopathy）
- D. 腕隧道症候群（carpal tunnel syndrome）
- E. 鎖骨下動脈竊血症候群（subclavian steal syndrome）

### Correct Answer: B

- Thoracic outlet syndrome指的是神經、血管要從胸腔出來到肢體端時，中途受到壓迫所產生的症候群，本題描述的是Costoclavicular syndrome (見下圖)。是Brachial plexus及Subclavian artery在通過Clavicle及1st rib交成的窄口，被壓迫時產生的症狀。


- Brachial plexus受壓迫時，主要無力側是上肢內側 (因ulnar nerve較median nerve容易受到壓迫)，若同行Subclavian artery上的交感神經一併受損，會合併血管收縮異常的症狀；反之，Sacral plexus受壓迫時，主要無力側是下肢外側 (因common peroneal nerve較tibialnerve容易受到壓迫)
- Brachial plexopathy：名稱很類似，通常指的是brachial plexus直接受到拉扯 (例如: 生產)、腫瘤壓迫 (如: 肺癌)、或是放射治療造成的brachial plexus病變。不會影響患側血壓
- Subclavian steal syndrome: 近端subclavian artery阻塞可能造成vertebral artery back flow，或是在做過CABG的病人造成internal thoracic artery (或稱mammary) back flow


Ref: Dunn’s topical diagnosis in neurology, 4’th edition, p102

## Question 187

關於自殺防治下列何者為非？

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- A. 各種用於預測自殺風險的篩檢問卷，對於未來自殺行為的陽性預測率 (positive predictive value) 都不高，很少超過20%
- B. 曾經因為自我傷害(self-harm)來急診的民眾，大約2%在未來一年會死於自殺
- C. 曾有研究指出，不幸自殺身亡的個案中，有80%在他們最後的語言溝通中，未曾顯露自殺的意念想法
- D. 實證研究均顯示：詢問病患是否有自殺意念，會大幅增加病患自殺風險
- E. 病人從精神科病房出院後一週內是自殺的高風險時段

### Correct Answer: D

- A. Wide variety of self-report and clinician-administered scales are available that measure various aspects of suicidal thoughts and behaviors as well as symptoms associated with suicide. ... However, their usefulness and generalizability in clinical practice are questionable. 大部分的量表都沒有在代表性族群裡接受測試。Few of these scales have been tested in prospective studies, and those thathave been tested have shown very low positive predictive validity and high rates of false positive findings.
- B.C. 查不到出處，不過D 明顯錯誤
- D. Asking depressed patients whether or not they have had thoughts of wanting to kill themselves does not plant the seed of suicide. To the contrary, it may be the first opportunity a patient has had to talk about suicidal ideation presenting of some time
- E. As with other psychiatric patients, the months after discharge from a hospital are a time of high risk

Reference: synopsis 23.1 suicide p.763-774, APA Practice guideline for the Assessment and Treatment of Patients With Suicidal Behaviors

## Question 188

關於下列各種抗焦慮藥物的特性描述何者為非？

---

- A. Diazepam作用速度(action of onset)快，鎮靜(sedation)效果明顯
- B. Lorazepam作用速度中等，無活性代謝物(no active metabolites)
- C. Alprazolam作用速度中等，較難戒斷停藥(difficult to withdrawal)
- D. Oxazepam作用速度快，具有半衰期極長之活性代謝物
- E. Clonazepam作用速度慢，美國FDA核准使用於恐慌症(panic disorder)

### Correct Answer: D

- A. 參見下方整理表格


- B. D. Lorazepam and oxazepam are metabolized only by conjugation with glucuronic acid with no intermediate steps and they have no active metabolites
- C. Generally, low-potency, long-acting BZD are considered to be safe and effective. High-potency, short-acting compounds such as the immediate release formulation of alprazolam, although effective as well, carry a higher risk of dependence and interdose rebound symptoms
- E. Two high-potency BZD, alprazolam and clonazepam have shown efficacy in the treatment of panic disorder compare with placebo in a number of studies and are FDA approved for the treatment of this condition.

Reference: Handbook of psychiatric drug therapy, Chapter 5 drugs for the treatment of anxiety disorders

## Question 189

關於鴉片類(opioid)製劑過量(overdose)的處置下列何者為非？

---

- A. 維護氣道(establish airway)為首要，有時需要插管或使用呼吸器
- B. Naloxone一般建議劑量0.4mg-2.0mg，可藉由肌肉注射，靜脈注射，或是氣管內管(endotracheal tube)給藥
- C. Naloxone靜脈給藥後 10 至 20 分鐘見效
- D. 若呼吸仍不理想Naloxone需重複給藥
- E. 當呼吸抑制解除後，每小時投與起始劑量的1/2到2/3做為維持治療

### Correct Answer: C

- A. Patients with stupor who have respiratory rates of 12 breaths per minute or less, ventilation should be provided with a bag-valve mask; chin-lift and jaw-thrust maneuvers, even intubation
- B+D+E. The initial dose of naloxone for adults is 0.4-2.0 mg IV; if there is no response, the dose should be increased every 2 minutes; maintenace: 0.2-1.0mg every 20 minutes to 2 hours
- C. IV use: onset less than 2 mins, and its apparent duration of action is 20 to 90 minutes上述為naloxone resuscitation原則, 每兩三分鐘加量直到有反應，最後一劑naloxone以後若有復原建議再觀察 2 小時 (待naloxone代謝完全, 如果還醒代表opioid也代謝得差不多了)，若為疼痛控制之病人, 可考慮較低劑量 (0.1-0.2mg, partial reversal), 以免大痛。

Reference: N Engl J Med. 2012 July 12; 367(2) Management of Opioid Analgesic Overdose

## Question 190

關於美國精神醫學會頒布「精神疾病診斷統計手冊第五版」(Diagnostic and Statistical Manual of Mental Disorders, Fifth edition: DSM-5)，下列何者不是酒精使用疾患(alcohol usedisorder)的診斷內容

---

- A. 酒精的耐受性(tolerance)
- B. 渴望飲酒(alcohol craving)
- C. 喝得比預期的還多還久(larger amount or longer)
- D. 反覆想戒酒但戒不掉
- E. 飲酒後產生重度憂鬱發作

### Correct Answer: E

* Alcohol use disorder diagnostic criteria酒精使用障礙症，過去一年內 11 取 2
A problematic pattern of alcohol use leading to clinically significant impairment or distress as manifested by at least two of the following, occurring within a 12-month period"

1. Alcohol is often taken in larger amounts or over a longer period than was intended比預計的還大量或長時間攝取酒精(C)
2. Persistent desire or unsuccessful efforts to cut down or control alcohol use持續渴望或無法戒除或是控制使用酒精(D)
3. A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effect花很多時間再買酒、喝酒或從其效應恢復
4. Cravings and urges to use alcohol (B)渴求或有強烈欲望想要喝酒
5. Recurrent alcohol use resulting in a failure to fulfill major role obligations at work, school or home 反覆喝酒導致無法完成職場、學校或居家的重要工作
6. Continuing to use, even when it causes problems in relationships儘管喝酒導致持續或反覆社交或人際問題，仍持續喝酒
7. Giving up important social, occupational or recreational activities because of alcohol use因喝酒放棄或減少重要的社交、職業或休閒活動
8. Recurrent alcohol use in situations in which it is physically hazardous在會傷害身體的情境下反覆喝酒
9. Continuing to use despite knowledge of having a persistent or recurrent physical or psychological problem that could have been caused or made worse by alcohol儘管知道喝酒恐引起持續或反覆生理或心理問題，仍持續喝酒
10. Needing increased amount of alcohol to achieve intoxication or desired effect (tolerance)(A)耐受性
11. Development of withdrawal symptoms, which can be relieved by taking alcohol or closely relatedsubstance(BZD) 戒斷症狀

E. 選項為 Substance(alcohol)-induced depressive disorder

Reference: DSM-5 substance-related and addictive disorders

## Question 191

關於失眠個案的非藥物處置衛教下列何者為非？

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- A. 刺激控制 (stimulus control)：有睡意的時候才去床上睡，睡不著而且焦慮的時候就離開床舖
- B. 睡眠衛生 (sleep hygiene)：臥室宜暗而安靜，時鐘宜移除於視線範圍外
- C. 放鬆治療 (relaxation therapy)：肌肉放鬆，呼吸訓練，沉思冥想(meditation)
- D. 認知治療 (cognitive therapy)：維持對於睡眠的合理期待，挑戰擔心失眠會引發災難性的過度預期心態E. 限制睡眠 (sleep restriction)：減少躺床時間至 3 個小時，並且與個案的生物週期(circadianrhythm)反向操作

### Correct Answer: E

- A. Stimulus control為一種deconditioning program，主要針對入睡的困難的惡性循環，做法便是在想睡時才躺到床上，並把床只用在睡眠上。
- B.C.D.皆正確
- E. Sleep restriction therapy is a strategy to increased sleep efficiency by decreasing the amount oftime spent awake while lying in bed, targeting patients lying awake in bed but unable to sleep. Restricting time in bed can help to consolidate sleep，但不建議少於四小時，白天也不宜補眠。

Reference: synposis p.543 sleep-wake disorders

## Question 192

關於老人虐待(elder abuse)在臨床上可能的線索，下列何者為非？

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- A. 一般老年人身上鮮少有自發性的瘀青(bruise)
- B. 老年人因跌倒而造成頭部的骨折較常見於眼窩(orbital)骨及鼻樑骨(nasal)，因為虐待毆打較常見於下顎(jaw)以及顴骨(zygomatic)骨折
- C. 被身體虐待(physical abuse)的老人，身上可能有許多傷口，而且處在不同的癒合階段
- D. 心理虐待(psychological abuse)的跡象包括老人被刻意隔絕於跟好朋友或信賴家人的互動接觸
- E. 長照機構內的老人虐待傷害，有可能是機構住民間互相攻擊所致

### Correct Answer: A

- A. 老人容易瘀青的幾個論點 Bruising that is common in aging and sun-exposed skin occurs on the dorsal aspects of hands and arms and is referred to as senile purpura. Steroid purpura occurs in areas of skin chronically treated with topical steroids, and systemic steroids increase purpura in areas of sun exposure and mild trauma. Atrophy in the skin and mucosa of menopausal women as a result of the decrease in estrogen levels
- B. The most common mechanisms resulting in facial fractures include falls (50%) and motor vehicle crashes (20%). These fractures are associated with significant morbidity and mortality, with up to 11% in-hospital mortality. The most common facial bone injured is the mandible (18%) (see Figures 12 and 13) and then the orbital floor (15%) and zygoma (15%). Providers should be aware that facial fractures along with upper extremity injuries are the most common presentations of elder abuse
- C.D.E. 明顯正確

Reference: Understanding the Medical Markers of Elder Abuse and Neglect: Physical Examination Findings

## Question 193

關於重度憂鬱症的診斷與治療，下列何者為非？

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- A. 起始階段主要是病人衛教以及選用可耐受的藥物
- B. 若抗憂鬱藥物治療反應不佳，需考慮個案之鑑別診斷是否為雙極性情感疾患
- C. 對於SSRI治療反應不佳 (treatment resistant) 的重度憂鬱症個案，換成SNRI的預期療效(efficacy)，比換成mirtazapine的預期療效顯著為高
- D. 治療重度憂鬱症個案若沒有達到完全緩解(full remission)，復發風險增加，自殺風險也增高
- E. 選用藥物的參考依據，還包括個案親人若也有重度憂鬱症，其親人的藥物治療反應

### Correct Answer: C

- A.E.正確
- B. Many patients who are bipolar in the depressed phase do not respond to treatment with standard antidepressant. 雙極性情感疾患於鬱期的治療選項不多，除了藥物選項不多，治療反應不佳，另外也需小心manic shift
- C. Initial non-responder，有許多治療策略，首先要考慮的是個案的compliance，其次可以考慮加劑量、換成其他種SSRI, 其他種類的的抗憂鬱劑(SNRI...)，並用抗憂鬱劑或是augmentationwith thyroid hormone/antipsychotics，但並沒有大規模、高證據力的研究證明哪一種方式、換哪一種藥效果較好
- D. 剛從suicidal depression中恢復的個案自殺風險特別高，因為他們恢復活力，可以將自殺計畫付諸實行(paradoxical suicide)。

Reference: synopsis ch8. Mood disorder, WFSBP Treatment of unipolar depressive disorders, part 1: Acute and continuation treatment of major depressive disorder (2013)

## Question 194

一 27 歲男性，因小腿一個快速變大的疼痛潰瘍 (如圖) 已有 2 週，至急診就醫。剛開始像個痘子。近 2 個月來，他有腹痛及腸道蠕動增加的問題。身體檢查並無發燒，vital sign 正常。潰瘍上並無化膿，也無廔管。請問最可能的診斷是：


---

- A. Calciphylaxis
- B. Ecthyma gangrenosum
- C. Necrotizing fasciitis
- D. Pyoderma gangrenosum
- E. Stasis ulcer

### Correct Answer: D

(快速變大、不像感染、無慢性病史)

A. Calciphylaxis
- Vascular calcification and cutaneous necrosis
- More commonly seen in ESRD, females
- Legs being the most common site
- Lesions start with tender red areas developing into a livedoid pattern. Solitary or multiple indurated plaques and/or nodules are then seen.
- Face and upper extremities are rarely involved.
-
- Irregular Areas of Dusky, Purplish
- Discoloration on the Skin of the Flank.

B. Ecthyma gangrenosum
- A rare skin infection caused by PsA
- In immunocompromised and critically ill patients
- Hemorrhagic vesicles and pustules that evolve into necrotic ulcers surrounded by a tender erythematous border
Ref: Indian Dermatol Online J. 2015 Sep-Oct; 6(5): 336 _–_ 338.

- Necrotic skin lesions

C. Necrotizing fasciitis
- Typically follows an injury to the involved site, most commonly in extremities
- Risk: DM, obesity, PAOD, IDU, alcohol, malnutrition, smoking, steroid, cancer, age
- Begins as a slightly inflamed area and dramatically progresses to fasciitis with systemic toxicity
- Blisters, bullae, crepitus, pain disproportionate to injury, foul-smelling “dishwater pus”
Ref: J Am Acad Orthop Surg 2009;17:174- 182

Developing blisters on the arm in necrotizing fasciitis


Necrotizing fasciitis of the arm.

D. Pyoderma gangrenosum (PG)

- Reaction to an internal disease? (inflammatory bowel, rheumatoid arthritis, hematologic cancers, granulomatosis with polyangiitis, monoclonal gammopathy, esp IgA, etc.)
- Begin as tender papules, papulopustules or vesicles, evolving into painful and enlarging ulcers
- Often regresses with cribriform mutilating scars
- Histopathology is nonspecific and may change according to different PG types and evolution.
- Some with extracutaneous disease (bones, cornea, CNS, heart, intestine, liver, lungs, muscle)
-
Ref: Clinical, Cosmetic and Investigational Dermatology 2015:8 285 _–_ 293


Ulcerative stage of PG, showing an elevated, violaceous, undermined border, with a necrotic and hemorrhagic base


Bullous variant


Cribriform scar after healing

E. Stasis ulcer
- The most common etiology of lower extremity ulceration
- Risk: old age, obesity, previous leg injuries, DVT,phlebitis
- Irregular, shallow, over bony prominences
- Complication: lower extremity varicosities, edema, venous dermatitis, cellulitis, osteomyelitis, and malignant change
Ref: Am Fam Physician. 2010;81(8):989-996, 1003


Wounds generally irregular and shallow

## Question 195

此 50 歲女性病患先有臉部潮紅現象，一年後後演 變成如圖所示之皮疹，遇熱時臉會更紅。最可能的診斷是：


---

- A. Systemic lupus erythematosus
- B. Solar dermatitis
- C. Rosacea
- D. Dermatomyositis
- E. Ofuji disease

### Correct Answer: C

臉潮紅與遇熱: 和血管擴張有關

A. Systemic lupus erythematosus


Malar rash (nasolabial sparing )


Discoid (papules w/ keratosis & plugging)


Vesiculobullous lesion

B. Solar dermatitis
- Stinging, itchy rash
- Develops within minutes after exposure
- Subside within a few minutes to hours
- Rx: avoid exposure, oral antihistamine
-

Ref: [http://www.dermnetnz.org/topics/solar-urticaria/](http://www.dermnetnz.org/topics/solar-urticaria/)

C. Rosacea

- Begins with a tendency to blush or flush, slowly spread beyond the nose and cheeks to the forehead and chin; with 4 subtypes; Usually 30-50y/o, with family Hx;
Ref: American Academy of Dermatology

Erythematotelangiectatic Rosacea
Facial redness, flushing, visible blood vessels


Papulopustular Rosacea: Acne-like breakouts


Phymatous Rosacea: Thickening skin (Rhinophyma if nose involved)


Ocular


D. Dermatomyositis


E. Ofuji disease/Eosinophilic pustular folliculitis (EPF)
- Peak incidence: 30-40y/o; etiology remains unknown
- A rare dermatosis, prone to recurrence and chronicity.
- Factors to induce: hypersensitivity, mites, fungal infections, Eos or T lymphocyte dysfunction, HIV, IRIS
- Papular pustules (1-2mm in diameter), then enlarge and merge, with formation of erythematous plaques.
- Usually follicular and pruritic, chronic, and recurrent, with centrifugal extension and central clearing.
-

- Take 7-10 days to heal and recur every 3- 4 weeks.
- Rx: topical steroid, Indomethacin

## Question 196

一位 70 歲女性，罹患糖尿病 10 年，未規則就醫服藥，一星期前在乳房下出現刺癢的紅色斑(如圖)，下列何者為最可能的診斷？


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- A. 膿痂疹（impetigo）
- B. 單純性皰疹病毒感染（herpes simplex virus infection）
- C. 皮膚念珠菌感染（cutaneous candidiasis）
- D. 毛囊炎（folliculitis）
- E. 體癬 (tinea corporis)

### Correct Answer: C

潮濕處，衛星小點



## Question 197

如圖所示之皮膚腫瘤是？


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- A. 棘細胞癌 (squamous cell carcinoma)
- B. 波文氏症 (Bowen's disease)
- C. 基底細胞癌 (basal cell carcinoma)
- D. 惡性黑素瘤 (malignant melanoma)
- E. 血管肉瘤 (angiosarcoma)
-
### Correct Answer: C






## Question 198

今年 7 月間，一位 33 歲男性，突然發生如圖所示之全身皮膚紅疹, 感覺日曬後會更紅更癢。以下何者有助於診斷：


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- A. 詢問過去 2 年規則使用的藥物名稱
- B. 詢問近二週新用之藥物名稱
- C. 做CBC 及differential count
- D. 做肝機能檢查
- E. 做光貼膚試驗 (photo-patch test)

### Correct Answer: B

- Photosensitivity workup: sites, distribution, timeline of onset related symptoms, family/medical/drug history and TOCC
- Photopatch test - 24 - 48 hours, suspicious material pasted on the skin + UV rays, positive if reddening or swelling in 24 hours, 比較常用在測試化妝品、防曬乳、香水、痠痛軟膏等塗抹物是否造成photosensitivity
-
Ref: DermNet New Zealand

Diseases Related to Photosensitivity
1. Actinic Prurigo
2. Chronic Actinic Dermatitis
3. Dermatomyositis
4. Lupus Erythematosus
5. Pemphigus
6. Polymorphic Light Eruption
7. Pseudoporphyria
8. Psoriasis
9. Rosacea
10. Solar urticaria, etc.

Medications Causing Photosensitivity Disorders
1. Amiodarone
2. Quinidine
3. Ciprofloxacin
4. Co-Trimoxazole
5. Dapsone
6. Tetracycline
7. Hydroxychloroquine
8. Furosemide
9. Hydrochlorothiazide
10. NSAIDs
11. 5 – Fluorouracil
12. Fenofibrate

## Question 199

一位 40 歲女性，近半年來在臉部、頸部與前胸部皮膚，出現如圖之表現。關於該患者診斷與治療的描述，何者正確？(請選出全部答案) 1.皮膚病理有明顯發炎反應，造成色素脫失 2.皮膚黑色素細胞消失或減少 3.應做甲狀腺功能與抗體的檢查 4.UVB1 (311nm) 窄波紫外光可促進色素回復。

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

### Correct Answer: D

Vitiligo Ref: American Academy of Dermatology; Am J Dermatopathol. 2008;30(2):112- 6
- Definite mechanism unknown (autoAb attacks melanocytes)
- Histopathology: more basal hypopigmentation and dermal inflammation than perilesional normal skin
(選項 1 好像也沒有太不對Am J Dermatopathol. 2008 Apr;30(2):112- 6 ，或許錯在色素脫失 melanopenic disorders是指albinism那一類色素減少但黑色素細胞正常之疾病，但vitiligo是黑 色素細胞變少)
- Can occur in: Skin(both sides), Hair (scalp, eyebrow, eyelash, beard), inside the mouth, genitals
- Occurs equally in people of all skin colors and races, and in both genders.
- Risk: family Hx, autoimmune disease, especially Hashimoto's disease or alopecia areata
- Rx: 1. Topical steroid (~45% partial response)
2. Light to repigment(Works best on the face; least effective on hands and feet, ~70% response, can disappear again)
3. Surgery 4. Unconventional treatment 5. Depigmentation



## Question 200

一 65 歲男性，先有鼻尖疼痛然後右眼週疼痛來就診。身體檢查發現vital sign都正常。在鼻尖及右眼週圍有底部紅腫的成簇小水皰。以下何者為恰當處置？ 1. 塗抹類固醇藥膏； 2. 立刻做ophthalmic consultation； 3. 做bacterial culture, 並給予cephalexin； 4. 給予口服valacyclovir; 5. IV push acyclovir

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

### Correct Answer: B

- Herpes Zoster Ophthalmicus
Patients with herpes zoster involving the first division of the trigeminal nerve typically present with unilateral pain and lesions on the forehead, periocular area, and nose. Without antiviral therapy, approximately 50 percent of these patients will have ocular complications (e.g., keratopathy, episcleritis, iritis, or stromal keratitis), some of which are potentially sight-threatening. Oral antiviral therapy reduces the frequency of late ocular complications from about 50 percent to 20 to 30 percent. Patients with herpes zoster ophthalmicus should be evaluated by an ophthalmologist who isexperienced in the management of corneal diseases.

Ref: N Engl J Med, 2002;347:5, Arffa RC, Grayson M. Grays _on’s Diseases of the cornea. 4th ed._