108年內專(151-200題)

# 108年內專(151-200題) ## Question 151: 下列何種抗體在診斷 rheumatoid arthritis 最具特異性？ --- - A.Anti-IgG - B.Anti-EB viral nuclear protein - C.Anti-collagen type II - D.Anti-CCP - E.Anti-proteoglycan ### Correct Answer: D 早期只有類風濕因子(rheumatoid factor，RF)可用來輔助診斷類風濕性關節炎(rheumatoid arthritis，RA)，但其特異性不足。Anti-CCP抗體(anti-cyclic citrullinated peptide antibodies抗環瓜氨酸抗體)臨床有一定的敏感度而特異度近95%。目前認為抗環瓜氨酸抗體對類風濕性關節炎不僅具有高靈敏度與特異性，且可在症狀出現前便存在，也可預測類風濕性關節炎疾病是否容易骨侵蝕破壞的預後指標。在最新的2010ACR criteria將Anti-CCP抗體納入重要診斷依據。延伸閱讀： 1. Serum IgM RF has been found in 75-80% of the patient with RA; but, a negative result does not excluded the presence of this disease. Also, the 1-2% of the healthy population could be detected serum RF 2. ![](https://hackmd.io/_uploads/SyiWmJIP2.png) 資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 321, p.2746 2. JENNIFER H. HUMPHREYS, SUZANNE M.M. VERSTAPPEN, CARLO A. SCIRE, TILL UHLIG, BRUNO FAUTREL, TUULIKKI SOKKA and DEBORAH P.M. SYMMONS, How Do We Classify Rheumatoid Arthritis in Established Disease — Can We Apply the 2010 American College of Rheumatology/European League Against Rheumatism Classification Criteria? , The Journal of Rheumatology December 2014, 41 (12) 2347-2351 ## Question 152: 下列有關 systemic sclerosis 的描述中,何者最為正確？ --- - A.最常出現的抗體為 anti-centromere antibodies - B.Anti-Jo-1 與 interstitial lung disease 無關 - C.Anti-topoisomerase 1 antibodies 為其生物標誌 - D.口服高量類固醇為治療皮膚硬化的首選藥物 - E.Raynaud's phenomenon 為在末期才會出現 ### Correct Answer: C (A) ANA test is positive in approximately 95% of patients with SSc, and therefore a 解 negative test should prompt consideration of other fibrosing illnesses (B) 有關, 詳見Kathryn Long, MD, Sonye K. Danoff, MD, PhD, 2019,interstitial lung disease in polymyositis and dermatomyositis, clin chest med, 40, 561-572 (C) 正確。在2013 ACR-EULAR criteria診斷SSc時，有含蓋Anti-body為診斷依據之一,其中包括Anti-centromere, Anti-topoisomerase 1 antibodies, 和anti‐RNA polymerase III，其中Anti-topoisomerase 1 antibodies即Anti-Scl70 為其診斷硬皮症的生物標誌。 (D) high dose glucocorticoid 會導致scleroderma renal crisis (SRC),通常會優先使用 immunosuppressive agent (E) Raynaud's phenomenon 分為primary Raynaud's phenomenon ,secondary Raynaud's phenomenon, primary Raynaud's phenomenon 主要影響15-30的女性, second Raynaud's phenomenon主要在老年人延伸閱讀： 1. Antitopoisomerase I (anti-Scl-70) antibody are generally associated with diffuse cutaneous SSc (dcSSc) and a higher risk of severe interstitial lung disease (ILD). 2. Anticentromere antibody (ACA) is usually associated with limited cutaneous SSc (lcSSc); only 5% of patients with dcSSc have ACA. 3. Anti-RNA polymerase III antibody are found in patients with dcSSc and are generally associated with rapidly progressive skin involvement as well as an increased risk for scleroderma renal crisis (SRC). These patients may also be at increased risk for concomitant cancer. 4. ![](https://hackmd.io/_uploads/ByXo7yLvn.png) 5. scleroderma renal crisis: Renal involvement is common in patients with SSc, with the most serious manifestation being scleroderma renal crisis (SRC), which occurs in a minority of patients. a.三個特點: ●Abrupt onset of moderate to severe hypertension that is typically associated with an increase in plasma renin activity ●Acute kidney injury (AKI) ●Urinalysis that is normal or reveals only mild proteinuria with few cells or Casts b.treatment: ACEI(captopril) 資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 323, p.2762-2763, p2766-2769 2. Uptodate “Clinical manifestations and diagnosis of systemic sclerosis (scleroderma) in adults”;” Overview of the treatment and prognosis of systemic sclerosis (scleroderma) in adults” 3.Kathryn Long, MD, Sonye K. Danoff, MD, PhD,2019,interstitial lung disease in polymyositis and dermatomyositis, clin chest med, 40, 561-572 ## Question 153: 下列有關 Sjogren's syndrome 的 extra-glandular manifestations 的描述中,何者最為正確？ --- - A.Erosive arthritis - B.Iritis/uveitis - C.Leukocytoclastic vasculitis - D.Oral cavity carcinoma - E.Primary biliary cholangitis ### Correct Answer: E 根據下列資料, 選項應為E Many organs other than the exocrine glands may be affected in patients with Sjögren's syndrome (SS); these include the skin and joints; the lungs, heart, and gastrointestinal tract, including the pancreas and liver; the kidneys, bladder, and gynecologic system; and both the peripheral nervous system (PNS) and central nervous system (CNS) Skin — ●Xerosis ●Purpura, associated with vascular or hematologic abnormalities ●Raynaud phenomenon ●Cutaneous vasculitis ●Annular erythema ●eyelid dermatitis and angular cheilitis Musculoskeletal — Joints —The arthropathy is usually symmetric, intermittent, nonerosive on plain radiographs. Muscles — A mild inflammatory myopathy (proximal muscle weakness) may occur in SS. Thyroid disease — autoimmune thyroiditis being most common. Lungs — Upper respiratory tract and airways – dry cough, hoarseness, and nasal dryness and crusting. Cystic lung disease – including pulmonary amyloidosis, lymphocytic interstitial pneumonitis, and lymphoma. Affected patients tend to be older and have anti-Ro/SSA antibodies. ●Interstitial lung disease – Interstitial lung disease in SS has several forms, including non-specific interstitial pneumonitis (NSIP), usual interstitial pneumonitis (UIP), lymphocytic interstitial pneumonitis (LIP), and cryptogenic organizing pneumonia (COP). NSIP is the most common histopathologic lesion but is a form of lung injury common to a variety of connective tissue diseases and hypersensitivity reactions. LIP can be a precursor to a bronchus-associated lymphoid tissue (BALT) lymphoma. Heart and cardiovascular system — Pericarditis and myocardial disease may occur, but are rarely evident clinically, and heart block is also rare but may occur in adults with SS. Heart block is rare in adult SS patients and is not consistently associated with anti-SSA/Ro antibodies. Congenital heart block may develop in the fetus of a pregnant woman with SS as a result of transplacental passage of anti-SSA/Ro antibodies. Gastrointestinal tract ●Oropharynx, upper gastrointestinal tract, and stomach – Dysphagia is common in SS, but its occurrence correlates poorly with salivary flow rates, arguing for mechanisms apart from a lack of saliva. Pharyngeal dysfunction and esophageal dysmotility have also been reported , and gastric emptying may be delayed as a result of autonomic dysfunction. Patients who have gastritis may be infected with Helicobacter pylori, an organism associated with mucosa-associated lymphoid tissue (MALT) lymphoma of the salivary glands in rare patients. ●Celiac disease – Celiac disease (gluten enteropathy) may be more prevalent in patients with SS than in the general population. ●Liver – SS is associated with hepatic abnormalities, including (usually mildly) abnormal biochemical tests and histologic changes of primary biliary cholangitis or autoimmune hepatitis. ●Pancreas – Since SS is a disease of exocrine glands, involvement of the pancreas would be expected, but is rarely evident clinically. SS has been reported in association with autoimmune sclerosing pancreatitis. Urogenital disease — immune-mediated renal disease, including interstitial nephritis, can occur in patients with SS; as may bladder dysfunction with symptoms of interstitial nephritis and gynecologic symptoms including vulvovaginal dryness, pruritus, and dyspareunia. ●Kidneys – Interstitial nephritis, renal tubular dysfunction leading to renal tubular acidosis and/or to decreased concentrating ability, and glomerular disease can occur in SS. ●Bladder – interstitial cystitis ●Vasculitis — Cutaneous vasculitis occurs in a significant minority of patients, but systemic necrotizing vasculitis is rare. Neurologic disease — Peripheral neuropathy affects approximately 10% of patients. Psychiatric disorders — Depression had a prevalence of 33 to 49% in small cohorts of primary SS patients. Hematologic manifestations — The hematologic manifestations of SS include cytopenias, especially mild anemia and leukopenia; hypergammaglobulinemia; and monoclonal gammopathies, cryoglobulinemia, and lymphoma, and are primarily seen in patients with autoantibodies (particularly anti-SSA or anti- SSB antibodies). Pregnancy — Pregnancy outcomes among patients with SS are generally similar to those of healthy women. However, women with SS who have anti-Ro/SSA antibodies are at risk for giving birth to babies with neonatal lupus. Among the manifestations of neonatal lupus, the greatest concern is congenital heart block. 資料來源： 1. Harrison’s principles of internal medicine, chapter 324, p.2771 2. Uptodate “Clinical manifestations of Sjögren's syndrome: Extraglandular diseasez” ## Question 154: 下列有關風濕免疫疾病的病因與結果的勾配關係中，何者最為正確？ --- - A.Anti-myeloperoxidase 引起 lupus nephritis - B.Anti-proteinase 3 引起 granulomatosis with polyangiitis - C.Viral infection 引起 Takayasu's arteritis - D.Immune complex 引起 giant cell arteritis - E.IgG4 引起 microscopic polyangiitis ### Correct Answer: B (A) Anti-myeloperoxidase: P- ANCA vasculitis:microscopic polyangiitis, eosinophilic 解 granulomatosis with polyangiitis,granulomatosis with polyangiitis, drug induced vasculitis (B) Anti-proteinase 3: C-ANCA vasculitis: eosinophilic granulomatosis with polyangiitis, granulomatosis with polyangiitis, microscopic polyangiitis(rarely) (C) Takayasu's arteritis:用 arteriograohy診斷 (D) giant cell ateritis: 1.clinical present: fever, anemia, high ESR level, headache, over 50 years old 2.diagnosis: temporal artery biopsy 與immune complex無關 (E) microscopic polyangiitis: p-ANCA 資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 326, p.2795-2797 2. Pocket medicine 7th edition, 8-17, 8-18, 8-19, 8-20 ## Question 155: 下列何種檢查對診斷 polyarteritis nodosa 最有幫助？ --- - A.Anti-elastase antibodies - B.Inflammatory parameters - C.Angiography - D.Anti-neutrophil cytoplasmic antibodies - E.Renal function test ### Correct Answer: C polyarteritis nodosa diagnosis: 解 1.angiography: aneurysm formation of involved small and medium- sized arteries in renal, hepatic, visceral vasculature 2.affected oragn biopsy 資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 326, p.2794 2. Pocket medicine 7th edition, 8-18 ## Question 156: 下列有關inflammatory muscle diseases 的描述中，何者最為正確？ --- - A.Inclusion body myositis 會引起末端肌肉的無力 - B.皮肌炎與腫瘤較無關聯性 - C.多發性肌炎與 B 細胞產生抗體有很大的關係 - D.本類疾病常常引起急性肌肉無力 - E.胃腸道的蠕動常受到影響 ### Correct Answer: A (A)正確。另inflammatory muscle diseases則是僅近端肢體無力。解 (B)24%與malignancy 有關 (C)T cell (D)通常是漸進式肌肉無力(數周至數月) (E)會造成dysphagia(影響到oropharyngeal striated muscle, upper )esophagus 資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 388, p.3509-3511 2. Pocket medicine 7th edition, 8-12 ## Question 157: 下列有關SLE的分類基準項目的組合中，何者最為正確? (1) chronic cutaneous vasculitis (2) RBC casts in urinalysis (3) anti-SSA/Ro (4) anti-phospholipid (5) positive direct Coomb's test (6) low serum complements (7) Raynaud's phenomenon (8) malar skin rash --- - A.(1)+(2)+(3)+(4) - B.(5)+(6)+(7)+(8) - C.(2)+(4)+(5)+(8) - D.(3)+(5)+(6)+(7) - E.(4)+(6)+(7)+(8) ### Correct Answer: C 考SLE ACR Criteria，選項(6)low serum complements為SLICC criteria，不在ACR 解 Criteria中。選項(1)(7)不在診斷標準內。根據下列表格: (A)(1)非需要 (B)(7)非需要 (C)正確答案 (D)(7)非需要 (E)(7)非需要 ![](https://hackmd.io/_uploads/BkjEO1Uv2.png) ![](https://hackmd.io/_uploads/rJmU_yUw3.png) 延伸閱讀： 1. 2012 SLICC criteria: 需要滿足17項中的四項, 其中臨床表現和免疫抽血項目至少需要一項, 或者病患anti-dsDNA antibodies(+) 加上腎臟切片診斷為狼瘡性腎炎, 即可診斷為紅斑性狼瘡。 2. 2019 EULAR/ACR criteria –were developed to improve detection of early- or new-onset SLE as well as improve the sensitivity and specificity compared with previous criteria. The classification for SLE requires the presence of a positive antinuclear antibodies (ANA) as an entry criterion. Additive criteria consist of seven clinical and three immunologic categories, each of which are weighted from 2 to 10. Patients are classified as having SLE with a score of 10 or more points. 3. In the validation cohort, which included patients with early disease, the EULAR/ACR criteria had a sensitivity of 96.1 % and a specificity of 93.4%, compared with the 96.7 % sensitivity and 83.7 % specificity of the Systemic Lupus International Collaborating Clinics (SLICC) criteria and the 82.8 % sensitivity and 93.4% specificity of the ACR criteria. ![](https://hackmd.io/_uploads/SyRd_yUD3.png) 資料來源： 1.Uptodate “Clinical manifestations and diagnosis of systemic lupus erythematosus in adults” ## Question 158: 下列有關rheumatoid arthritis 的extra-articular manifestations 中，何者最為正確？ (1)Uveitis (2)cervical myelopathy (3)oral mucosa ulcer (4)Felty's syndrome (5)mechanical hand (6)rheumatoid nodule (7)inflammatory bowel diseases (8)episcleritis --- - A.(2)+(4)+(8) - B.(1)+(2)+(3) - C.(4)+(5)+(6) - D.(6)+(7)+(8) - E.(2)+(3)+(6) ### Correct Answer: A 解 Extra-articular manifestation of Rheumatoid arthritis 1.ocular- episcleritis, scleritis, uveitis, keratoconjunctivitis sicca 2.oral- xerostomia, periodontitis 3.lung- pleuritis, pleural effusion, interstitial fibrosis, pulmonary nodules, bronchiolitis obliterans, and organizing pneumonia 4.cardiac- pericarditis, myocarditis, coronary artery disease, cardiomyopathy, arrthymia, mitral regurgitation 5.renal-membranous nephropathy, secondary amyloidosis 6.endocrine-hypoandrogenism 7.skin- rheumatoid nodules, skin ulcers, purpura, pyoderma gangrenosum 8.neurologic- carpal tunnel syndrome, cervical myelopathy or radiculopathy 9.hematologic- anemia of chronic inflammation, Felty's syndrome, neutropenia, splenomegaly, large granular lymphocyte leukemia 10.vasculitis 11.skeletal-osteoporosis 依據上述資料, A為正解資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 321, p.2740, Fig 321-2 2. Pocket medicine 7th edition, 8-3 3. Uptodate “Overview of the systemic and nonarticular manifestations of rheumatoid arthritis” ## Question 159: 下列有關axial spondyloarthritis 的發炎性下背痛分類基準的組合中，何者最為正確？ (1) Age>40 year-old (2) HLA-B27 (+) (3) acute lumbago (4) relief after exercise (5)半夜或清晨的酸痛僵硬>30分 (6) 白天休息之後會和緩 (7) 腰部脊椎會變直 (8)照MRI幫助不大 --- - A.(1)+(2)+(3) - B.(4)+(5)+(7) - C.(2)+(4)+(8) - D.(3)+(6)+(7) - E.(6)+(7)+(8) ### Correct Answer: B 解題：Axial spondyloarthritis (also often referred to as axSpA) is a chronic, autoinflammatory disease predominantly affecting the axial skeleton (sacroiliac joints and spine). The most known member of the axial spondyloarthritis disease family is ankylosing spondylitis. 根據以下表格 (1) Age>40 year-old錯誤。通常小於45歲，並列為重要診斷依據之一。 (2) 診斷標準裡不一定需要HLA-B27(+) (3) 通常會是慢性下背疼痛超過三個月 (4) 正確 (5) 正確 (6) 運動後緩和 (7) 正確 (8) 在without radiographic sacroilitis的人中，MRI可幫助診斷分類 ![](https://hackmd.io/_uploads/r1T5t1UD3.png) ![](https://hackmd.io/_uploads/rJ3sY1Uv2.png) ![](https://hackmd.io/_uploads/Hypht18vh.png) ![](https://hackmd.io/_uploads/rk-AKkIPh.png) 資料來源： 1. Harrison’s principles of internal medicine 18th edition, chapter 325, p.2774-2777 2. Joel D. Taurog, M.D., Avneesh Chhabra, M.D., and Robert A. Colbert, M.D., Ph.D., 2016, Ankylosing Spondylitis and Axial Spondyloarthritis, N Engl J Med 2016;374:2563-74. 3. Nilasha Ghosh and Eric M. Ruderman, Nonradiographic axial spondyloarthritis:clinical and therapeutic relevance, Ghosh and Ruderman Arthritis Research & Therapy (2017) 19:286 ## Question 160: 一位病人抽血檢查顯示Hb為10.2 gm/dL，MCV 75 fL，reticulocyte 0.8%，ferritin 78 ng/mL (參考值5-200)，iron 41 μg/dL(參考值50-200)，TIBC 230 μg/dL(參考值260-590)，白血球及血小板數正常。這位病人最可能的診斷為： --- - A.Iron deficiency anemia - B.Thalassemia - C.Anemia of chronic disease - D.Folic acid deficiency anemia - E.Hemolytic anemia ### Correct Answer: C ![](https://hackmd.io/_uploads/S17-o8vvh.png) ⚫ Iron deficiency anemia – Important discriminating features are a low serum ferritin concentration, an increased total iron binding capacity (transferrin), and low serum iron concentration, resulting in a low transferrin saturation. For clinicians making this diagnosis, it is mandatory to determine the cause of the iron deficient state (eg, occult colonic carcinoma, excessive menstrual losses). ⚫ Alpha or beta thalassemia minor – Adults with thalassemia are most often heterozygotes for the alpha or beta forms of this syndrome, and may be only minimally anemic. A family history is therefore often negative. Physical examination may reveal splenomegaly; the peripheral smear shows varying degrees of hypochromia, microcytosis, target cells, tear-drop forms, and basophilic stippling. The RBC count may actually be increased; uncomplicated patients have normal or increased iron stores. ⚫ The diagnosis of beta thalassemia trait can often be made by demonstrating increased levels of hemoglobin A2 on hemoglobin electrophoresis or liquid chromatography (HPLC), while molecular methods are usually required for the diagnosis of the alpha thalassemia variants. ⚫ Anemia of inflammation – The hallmarks of this condition include a low serum iron, low total iron binding capacity (transferrin), and a normal to increased serum ferritin concentration. Although hypochromic and microcytic red cells can be found in these patients, a low MCV is most frequently seen only in those patients with hepatoma or renal cell carcinoma. 資料來源： UpToDate Approach to the adult with anemia ## Question 161: 下列有關陣發性夜間血色素尿的臨床表現何者是錯的？ --- - A.PIG A gene mutation - B.CD55 and CD59 deficiency on blood cells - C.Hypercoagulable state - D.Intravascular hemolysis - E.Bilirubinuria ### Correct Answer: E EPIDEMIOLOGY ⚫ PNH is a rare disorder. range of 1 to 10 cases per million population (although this may be an underestimate as a subset of patients are likely to remain undiagnosed) ⚫ mostly a disease of adults. The median age of onset is in the thirties. ⚫ affects males and females nearly equally. Even though the vast majority of cases are associated with mutation of PIGA (a gene on the X chromosome), PNH results from an acquired mutation in a somatic cell rather than a germline cell; somatic cells, including hematopoietic stem cells, only use one X chromosome (the other X chromosome being "lyonized") ⚫ There is no known ethnic or geographic distribution. However, ethnic/geographic factors do appear to modify the risks of thrombosis and bone marrow failure in individuals with PNH CLINICAL MANIFESTATIONS ⚫ PNH is associated with a wide range of clinical findings. In general, the severity of clinical findings is thought to correlate with the size(s) of the PNH clone(s) in untreated patients; however, some patients may be relatively asymptomatic with a large PNH clone. ⚫ Many patients present with unexplained hemolytic anemia and associated symptoms, including fatigue, jaundice, and red/pink/black urine. Decreased bone marrow function in some individuals may further exacerbate anemia and cause other cytopenias. ⚫ Another presentation of PNH is with thrombosis in an atypical location, such as an abdominal or cerebral vein, due to a hypercoagulable state induced by complement activation, free hemoglobin in the bloodstream, and possibly other procoagulant mechanisms. ⚫ Some patients have more unusual presentations in which nonspecific symptoms predominate. Intravascular hemolysis releases free hemoglobin into the circulation, and the resulting depletion of nitric oxide (NO) may cause symptoms of increased smooth muscle tone including dysphagia, abdominal pain, or erectile dysfunction. Over time, hemoglobinemia may also cause renal insufficiency and pulmonary hypertension. Laboratory abnormalities — Laboratory findings in PNH include typical findings of hemolytic anemia, loss of GPI-anchored proteins, and findings associated with organ damage from hemolysis and/or thrombosis. Findings of non-antibody-mediated (Coombs-negative) intravascular hemolysis include the following: ⚫ Anemia ⚫ Increased reticulocyte count ⚫ Increased lactate dehydrogenase (LDH) and bilirubin ⚫ Decreased haptoglobin ⚫ Free serum hemoglobin with pink/red serum ⚫ Hemoglobinuria with pink/red urine, positive dipstick for heme, and negative sediment for red blood cells ⚫ Negative direct antiglobulin (Coombs) test (DAT) ⚫ Hypocellular, normocellular or hypercellular bone marrow, often with erythroid hyperplasia; erythroid dysplasia is not uncommon ⚫ Findings of iron deficiency may be seen in some patients due to excessive iron loss from hemoglobinuria and hemosiderinuria (eg, low iron, low ferritin, increased transferrin, absent bone marrow iron) Flow cytometry including FLAER — Flow cytometry is the most useful and accepted method to confirm the diagnosis of PNH in the appropriate clinical setting. Some clinicians also use annual flow cytometry to screen patients with an underlying bone marrow disorder (eg, AA, MDS) for the development of subclinical PNH. Flow cytometry is performed by incubating the patient's peripheral blood cells with fluorescently-labeled monoclonal antibodies that bind to glycosylphosphatidylinositol (GPI)-anchored proteins, which are reduced or absent on blood cells in PNH. GPI-linked proteins that can be assayed include CD59 and CD55, as well as CD14, CD15, CD16, CD24, CD45, and CD64. Each laboratory uses a defined cocktail of antibodies; most also incorporate FLuorescent AERolysin (FLAER), a reagent derived from the bacterial toxin aerolysin, which binds directly to the GPI anchor; proaerolysin is the inactive precursor of aerolysin, which also binds to GPI 資料來源： UpToDate Clinical manifestations and diagnosis of paroxysmal nocturnal hemoglobinuria ## Question 162: 一位75歲病人長期因高血壓一直規則看診。最近抽血檢查無意中發現血清中有IgG/kappa單株球蛋白(monoclonal gammopathy)，IgG 3700 mg/dL，其他血液檢查如血紅素、白血球及血小板數、血鈣及腎功能正常；骨髓檢查顯示漿細胞為35%，骨骼檢查無蝕骨病變。此位病人最恰當的診斷為？ --- - A.Monoclonal gammopathy of undetermined significance - B.Smoldering multiple myeloma - C.Symptomatic multiple myeloma - D.Waldenstrom's macroglobulinemia - E.Light chain disease ### Correct Answer: B Plasma cell dyscrasias are heterogeneous disorders arising from the proliferation of a monoclonal population of plasma cells. Some of these disorders can present serendipitously as benign processes that can be observed; others are highly aggressive and require immediate intervention. The most common plasma cell dyscrasia is monoclonal gammopathy of undetermined significance (MGUS), a benign condition that can be observed. Related disorders include smoldering multiple myeloma (SMM), multiple myeloma (MM), …, Waldenström macroglobulinemia (WM), primary amyloid light-chain (AL) amyloidosis, …, etc.. A. MGUS is a clinically asymptomatic premalignant clonal plasma cell or lymphoplasmacytic proliferative disorder. It is defined by the presence of a serum monoclonal protein (M protein) at a concentration <3 g/dL, a bone marrow with <10 percent monoclonal plasma cells, and absence of end-organ damage (lytic bone lesions, anemia, hypercalcemia, renal insufficiency, hyperviscosity) related to the proliferative process. B. SMM is defined as a M protein ≥3 g/dL and/or 10 to 60 percent bone marrow plasma cells but no end-organ damage that can be attributed to the underlying plasma cell disorder or other myeloma-defining events, and no amyloidosis C. The diagnosis of MM requires fulfillment of the following criterion: ⚫ Clonal bone marrow plasma cells ≥10 percent or biopsy-proven bony or soft tissue plasmacytoma . Plus one of the following: ⚫ Presence of related organ or tissue impairment (often recalled by the acronym CRAB) ◼ Anemia – Hb <10 g/dL or >2 g/dL below normal. ◼ Hypercalcemia – Serum calcium >11 mg/dL ◼ Renal insufficiency – Estimated or measured creatinine clearance <40 mL/min or serum creatinine >2 mg/dL. (Creatinine clearance is the preferred measure of renal insufficiency.) ◼ Bone lesions – One or more osteolytic lesions ≥5 mm in size on skeletal radiography, MRI, CT, or PET/CT. In the absence of osteolytic lesions, the following are not sufficient markers of bone lesions: increased FDG uptake on PET, osteoporosis, or vertebral compression fracture. When a diagnosis is in doubt, biopsy of the bone lesion should be considered. Manifestations of non-CRAB end-organ damage (eg, hyperviscosity, recurrent bacterial infections, AL amyloidosis, peripheral neuropathy) are nonspecific and not diagnostic of MM. ⚫ Presence of a biomarker associated with near inevitable progression to end-organ damage – One or more of the following: ◼ ≥60 percent clonal plasma cells in the bone marrow. ◼ Involved/uninvolved FLC ratio of 100 or more (provided involved FLC level is at least 100 mg/L). ◼ MRI with more than one focal lesion (involving bone or bone marrow). Most but not all patients will have an M protein in serum and/or urine. Approximately 40 percent of patients with symptomatic MM will have an M protein of less than 3 g/dL. In true nonsecretory MM (approximately 3 percent of MM), an M protein will not be detectable in the serum or urine with immunofixation D. The diagnosis of WM is made based on an evaluation of a bone marrow biopsy specimen, analysis of the serum protein components, and consideration of the clinical scenario. To make a diagnosis of WM, the following criteria must be met: ⚫ An IgM monoclonal gammopathy (of any size) must be present in the serum. ⚫ ≥10 percent of the bone marrow biopsy sample must demonstrate infiltration by small lymphocytes that exhibit plasmacytoid or plasma cell differentiation (lymphoplasmacytic features or lymphoplasmacytic lymphoma) with an intertrabecular pattern. The requirement for ≥10 percent marrow infiltration is to differentiate patients with WM from patients with IgM MGUS. ⚫ This infiltrate should express a typical immunophenotype (eg, surface IgM+, CD5-/+, CD10-, CD11c-, CD19+, CD20+, CD22+, CD23-, CD25+, CD27+, FMC7+, CD103-, CD138-). The plasmacytic component will be CD138+, CD38+ and CD45- or dim. The MYD88 L265P gene mutation has been identified in over 90 percent of patients with WM, and can be of help on differentiating WM from other conditions E. Diagnostic criteria for AL amyloidosis require the presence of all of the following four criteria: ⚫ Presence of an amyloid-related systemic syndrome (eg, renal, liver, heart, gastrointestinal tract or peripheral nerve involvement). In order to be included as a diagnostic criterion, the organ damage must be felt to be related to amyloid deposition and not to another common disease, such as diabetes or hypertension. ⚫ Positive amyloid staining by Congo red in any tissue (eg, fat aspirate, bone marrow or organ biopsy) or the presence of amyloid fibrils on electron microscopy. ⚫ Evidence that the amyloid is light chain-related established by direct examination of the amyloid using spectrometry-based proteomic analysis or immunoelectron microscopy. ⚫ Evidence of a monoclonal plasma cell proliferative disorder (eg, presence of a serum or urine M protein, abnormal serum free light chain ratio, or clonal plasma cells in the bone marrow). 資料來源： UpToDate Diagnosis of monoclonal gammopathy of undetermined significance Smoldering multiple myeloma Epidemiology, pathogenesis, clinical manifestations, and diagnosis of Waldenström macroglobulinemia Multiple myeloma: Clinical features, laboratory manifestations, and diagnosis Clinical presentation, laboratory manifestations, and diagnosis of immunoglobulin light chain (AL) amyloidosis ## Question 163: Ibrutinib對某些淋巴惡性疾病如chronic lymphocytic leukemia, mantle cell lymphoma等非常有效。它的作用機轉為何？ --- - A. Phosphoinositide-3 kinase (PI3K) inhibitor - B. Burton tyrosine kinase (BTK) inhibitor - C. B-cell lymphoma 2 (BCL-2) inhibitor - D. Anti-CD79a monoclonal antibody - E. Anti-CD19 monoclonal antibody ### Correct Answer: B Initial management of chronic lymphocytic leukemia Our preferred initial therapy depends on a genetic risk stratification of the tumor and an assessment of patient fitness: ⚫ 17p deletion and/or TP53 mutation – Patients are at high risk of either not responding to initial treatment with chemoimmunotherapy, or relapsing soon after achieving remission, and should be encouraged to participate in clinical trials. For these patients, we recommend initial treatment with targeted therapy (ie, ibrutinib-based therapy [BTK inhibitor] or venetoclax-based therapy [BCL2 inhibitors]) rather than chemoimmunotherapy, regardless of patient age IGHV unmutated (without 17p deletion or TP53 mutation) – targeted therapy rather than chemoimmunotherapy due to a clear improvement in progression-free survival (PFS), with a demonstrated OS benefit in some trials. The choice among targeted agents is strongly dependent on patient comorbidities and preferences. We have longer-term data regarding the efficacy and toxicity of ibrutinib-based therapy. Ibrutinib is an oral therapy that is given continuously until progression. While response rates are high, few patients achieve measureable residual disease (MRD) negativity. In contrast, MRD negativity can be achieved by the majority of patients treated with a fixed duration of venetoclax plus obinutuzumab. ⚫ IGHV mutated (without 17p deletion or TP53 mutation) – For these patients, PFS and OS appear to be similar regardless of whether chemoimmunotherapy or targeted therapy is used. Long-term follow-up of prospective trials have demonstrated that a subset of patients with IGHV-mutated CLL treated with chemoimmunotherapy obtain prolonged durable remissions, possibly suggesting cure. If chemoimmunotherapy is chosen, the preferred regimen depends on clinical fitness. In order of decreasing efficacy and increasing tolerability, options include: ◼ Fludarabine, cyclophosphamide, and rituximab (FCR) ◼ Bendamustine plus rituximab ◼ Chlorambucil plus obinutuzumab Early relapse — Patients with a PFS less than the median expected for a treatment regimen are considered to have "early relapse." This includes patients progressing within two to three years following initial treatment with FCR and within one year after initial treatment with other chemoimmunotherapy regimens. ⚫ For patients with early relapse, we recommend targeted therapy (eg, ibrutinib, venetoclax with or without rituximab) rather than retreatment with the prior therapy or a trial of another chemoimmunotherapy regimen. ◼ PI3K inhibitors: Idelalisib: ◆ The combination of idelalisib plus rituximab is another treatment option for patients with refractory or early relapsing CLL. The following risks should be noted: ◆ Idelalisib is associated with an increase in opportunistic infections and the manufacturer suggests prophylaxis for PJP and monitoring for CMV. ◆ Idelalisib carries boxed warnings regarding an increased risk of fatal and/or serious hepatotoxicity, diarrhea, colitis, intestinal perforation, and pneumonitis. Idelalisib has also resulted in hypertriglyceridemia, hyperglycemia, ALT elevations, and AST elevations. Hepatic function should be evaluated prior to and during treatment. Late relapse — Patients progressing greater than two to three years after initial treatment with FCR or more than one year after initial treatment with other chemoimmunotherapy regimens may be considered to have late relapse. ⚫ For most patients, we suggest a targeted therapy (eg, ibrutinib, venetoclax with or without rituximab) rather than retreatment with the same regimen that provided that initial response (Grade 2C). 資料來源： UpToDate Selection of initial therapy for symptomatic or advanced chronic lymphocytic leukemia Treatment of relapsed or refractory chronic lymphocytic leukemia ## Question 164: 一位63歲病人被診斷為嚴重型再生不良性貧血，經過Anti-thymocyte globulin及cyclosporine治療後反應不佳，仍全血球低下，經常需要輸血。此時最有效之治療方式為何？ --- - A. Eltrombopag - B. Danazol - C. Steroid - D. G-CSF - E. Erythropoietin ### Correct Answer: A REFRACTORY DISEASE Immunosuppressive therapy (IST) fails to produce a hematologic response in approximately one-fourth of patients with severe AA. It is not known whether refractory disease represents ongoing immune attack on hematopoietic cells (ie, a failure of immunosuppression) or a persistent stem cell deficiency. Therapies directed at either (or both) of these problems may be useful. Potential approaches include eltrombopag, alemtuzumab (alone or in combination with cyclosporin), or high dose cyclophosphamide. ⚫ Eltrombopag — Eltrombopag is our first choice for the treatment of refractory disease. ⚫ Alemtuzumab (refractory disease) — Alemtuzumab (Campath) is another good option for treating refractory disease that does not respond to eltrombopag plus IST, or for patients who do not have access to (or whose disease does not respond to) eltrombopag. Alemtuzumab is an immunosuppressive humanized monoclonal antibody directed against CD52, which is present on lymphocytes and other hematopoietic cells. Alemtuzumab has shown efficacy in refractory disease and as initial therapy, either alone or in combination with cyclosporin A (CsA) ⚫ Horse (or rabbit) ATG if not used previously — Patients with refractory disease who did not receive horse ATG as part of initial treatment may benefit from treatment that includes horse ATG, and those whose disease did not respond to horse ATG may benefit from a regimen using rabbit ATG. ⚫ Allogeneic HCT — It may be possible to perform allogeneic hematopoietic cell transplantation (HCT) in some patients with refractory disease, including those who did not initially have an available donor but subsequently found an HLA-matched unrelated donor or decided to use a mismatched or haploidentical donor. 資料來源： UpToDate Treatment of aplastic anemia in adults ## Question 165: 一位病人血液檢查發現血液相異常，血液抹片如圖所示。此病人最可能得了什麼病？ ![](https://hackmd.io/_uploads/r1UUaIvPn.png) --- - A. 慢性淋巴增生性疾病 - B. 慢性骨髓性白血病 - C. 急性前骨髓細胞白血病 - D. 急性單核細胞白血病 - E. 急性淋巴芽細胞白血病 ### Correct Answer: C Acute promyelocytic leukemia— APL is characterized by the presence of atypical promyelocytes in the bone marrow and peripheral blood. Promyelocytes are large (usually >20 microns in diameter) myeloid precursors with variable morphology. Often there is a high nucleus to cytoplasmic ratio, fine chromatin, and prominent nucleoli. The cardinal feature of the promyelocyte is the presence of many violet granules in the cytoplasm with either a dense or coarse pattern, often obscuring the nucleus. The cells of APL differ morphologically from those of normal promyelocytes in that they are larger and typically have creased, folded, bilobed, kidney-shaped, or dumb-bell shaped nuclei ![](https://hackmd.io/_uploads/S1Ct6LDP3.png) 延伸閱讀： Lymphoproliferative disease of large granular lymphocytes — Lymphoproliferative disease of the large granular lymphocyte is a relatively rare atypical lymphocytosis characterized by the presence in the blood of >2000/microL large lymphocytes with slightly eccentric nuclei and abundant pale-blue cytoplasm containing many azurophilic granules. Phenotypically these cells can be divided into expansions of CD3+/CD8+/CD4- T cells or CD3-/CD56+ NK cells that are usually clonal. These patients rarely may present in childhood but usually present in the fourth or fifth decade of life with autoimmune manifestations and neutropenia. While they can have absolute lymphocytosis, they can also have normal total lymphocytes with an increased percent of cytotoxic lymphocytes. ![](https://hackmd.io/_uploads/r1Hj6Lww3.png) Chronic myeloid leukemia The peripheral smear typically demonstrates a leukocytosis with a median white count of approximately 100,000/microL (range 12,000 to 1,000,000/microL). The white blood cell differential typically shows virtually all cells of the neutrophilic series, from myeloblasts to mature neutrophils with peaks in the percent myelocytes and segmented neutrophils. Blasts typically account for less than 2 percent. The presence of a greater percent of myelocytes than the more mature metamyelocytes ("leukemic hiatus" or "myelocyte bulge") is one of the classic findings in CML. The granulocytes of chronic phase are morphologically normal with no evidence of dysplasia, but dysplasia can develop in more advanced disease, and particularly in accelerated phase. ![](https://hackmd.io/_uploads/HkR36UwP3.png) Acute monoblastic and monocytic leukemia ⚫ In acute monoblastic leukemia, the vast majority of the cells (>80 percent) are monoblasts. Monoblasts are large with abundant, moderately to intensely basophilic cytoplasm, which may demonstrate pseudopod formation, scattered fine azurophilic granules, and vacuoles. Nuclei are round with delicate lacy chromatin and one or more large prominent nucleoli. ⚫ In acute monocytic leukemia, promonocytes and mature monocytes predominate with less than 80 percent monoblasts. Promonocytes are large with less basophilic and sometimes more obviously granulated cytoplasm with occasional large azurophilic granules and vacuoles. The nucleus is irregular with a delicately convoluted configuration ![](https://hackmd.io/_uploads/ByW0TUDv2.png) Acute lymphoblastic leukemia Morphology may vary from small cells with scant cytoplasm, condensed nuclear chromatin, and indistinct nucleoli to larger cells with moderate amounts of cytoplasm, dispersed chromatin, and multiple nucleoli; coarse azurophilic cytoplasmic granules may be present, but Auer rods are absent. The appearance of lymphoblasts in biopsy specimens is relatively uniform, but the cells may include round, oval, indented, or convoluted nuclei, finely dispersed chromatin, and nucleoli that can range from inconspicuous to prominent. ![](https://hackmd.io/_uploads/S1gy08ww3.png) 資料來源： UpToDate Clinical manifestations, pathologic features, and diagnosis of acute promyelocytic leukemia in adults Approach to the child with lymphocytosis or lymphocytopenia Clinical manifestations and diagnosis of chronic myeloid leukemia Classification of acute myeloid leukemia Overview of the clinical presentation and diagnosis of acute lymphoblastic leukemia/lymphoma in children ## Question 166: 一位58歲病人因大腿疼痛有硬塊應診，超音波檢查顯示有肌肉內血腫塊，經實驗室檢查診斷為後天A型血友病(acquired hemophilia A)。以下與此病相關的敘述何者有誤？ --- - A. 多因免疫異常所引起(immune mediated) - B. Prothrombin time正常 - C. Thrombin time正常 - D. Mixing test將病人與正常人之血漿混合後2小時後檢驗，aPTT會恢復正常 - E. 可以用activated prothrombin complex concentrate (aPCC)治療 ### Correct Answer: D VIII INHIBITORS The most common autoantibodies that affect clotting factor activity and lead to a bleeding disorder are directed against, and interfere with, the activity of factor VIII, a condition also called acquired hemophilia A. Although there are no large series describing the immunoglobulin class of the factor VIII autoantibodies, most have been IgG antibodies that do not bind complement. The reasons for the production of factor VIII autoantibodies in a particular individual are not clear, but may involve the presence of certain gene polymorphisms (eg, HLA, CTLA4) and/or autoreactive CD4+ T lymphocytes Diagnosis — The sudden presence of large hematomas or extensive ecchymoses in an older individual without significant trauma or known bleeding disorder should always raise the clinical suspicion of an acquired factor VIII inhibitor. ⚫ Coagulation tests — prolonged aPTT and a normal PT. ⚫ Inhibitor screen (mixing test) — The primary initial diagnostic test for a factor VIII inhibitor is the mixing test or inhibitor screen. In this assay, varying amounts of patient plasma and pooled normal plasma are mixed and the aPTT measured. After mixing, measurement of the aPTT should be performed not only immediately but also after incubation at 37ºC for one to two hours. The second measurement is necessary to detect factor VIII inhibitors with slow reaction kinetics. Correction of the prolonged aPTT suggests a factor deficiency or VWD, while persistent prolongation of the aPTT indicates the presence of an inhibitor. The mixing test will establish whether an inhibitor is present but will not identify the inhibitor's specificity. The next step is adding a source of phospholipid to the mixed plasma. Correction of the aPTT suggests the presence of antiphospholipid antibodies. If the aPTT does not correct, the Bethesda assay is performed. The Bethesda assay both establishes the diagnosis of a factor VIII inhibitor and quantifies the antibody titer. By standardizing the strength of factor VIII inhibitors, this assay also permits comparison between different treatment regimens. ⚫ Bethesda assay — In the Bethesda assay, serial dilutions of patient plasma are incubated with pooled normal plasma at 37ºC for two hours; factor VIII activity is then measured using a clotting assay as one would in a patient with hereditary factor VIII deficiency. The reciprocal dilution of patient plasma that results in 50 percent factor VIII activity is defined as one Bethesda unit (BU). The stronger the inhibitor, the greater the dilution required to allow for factor VIII activity. TREATMENT OF FACTOR VIII INHIBITORS Control of active bleeding — Treatment strategies to control active bleeding include the use of desmopressin (DDAVP), factor VIII concentrates, activated prothrombin complex concentrates (aPCCs; eg, factor eight inhibitor bypassing activity [FEIBA]), recombinant human factor VIIa, and recombinant porcine sequence factor VIII concentrate. Eliminating the inhibitor—To eliminate factor VIII inhibitors, we recommend the use of —prednisone at an initial oral dose of 1 mg/kg per day —in all patients (Grade 1B). Based upon weak evidence from the literature and our own experience, we suggest that oral cyclophosphamide (2 mg/kg per day) be added to the initial prednisone treatment regimen (Grade 2C). 資料來源： UpToDate Acquired inhibitors of coagulation ## Question 167: 冷凍沈澱(Cryoprecipitate)可用於治療何種病人？ (1) Hypofibrinogenemia (2) Hypoalbuminemia (3) Hemophilia A (4) von Willebrand disease --- - A. (1)+(2) - B. (1)+(3) - C. (1)+(2)+(3) - D. (1)+(3)+(4) - E. (1)+(2)+(3)+(4) ### Correct Answer: D 解題： ⚫ Cryoprecipitate contains fibrinogen (factor I), factor VIII, fibronectin, factor XIII, and von Willebrand factor (VWF). ⚫ Cryoprecipitate remains an effective therapy for bleeding in patients with fibrinogen disorders, liver disease, disseminated intravascular coagulation (DIC), or uremia after desmopressin are found to be ineffective. Cryoprecipitate may also be used in the rare setting of bleeding in individuals with hemophilia A, von Willebrand disease (VWD), or factor XIII deficiency when a purified/recombinant factor is unavailable. Cryoprecipitate is also used during pregnancy in some individuals with inherited fibrinogen disorders. 資料來源： UpToDate Clinical use of Cryoprecipitate ## Question 168: 下列有關淋巴瘤及其相對應之染色體變異，何者是正確的？ (1) Follicular lymphoma: t(14;18) (2) Mantle cell lymphoma: t(3;14) (3) Burkitt lymphoma: t(8;14) --- - A. (1) - B. (3) - C. (1)+(3) - D. (2)+(3) - E. (1)+(2)+(3) ### Correct Answer: C Mantle cell lymphoma— MCL are highly associated with a (11;14) translocation that dysregulates the cyclin D1 gene (CCND1). 延伸閱讀： Burkitt lymphoma— Genetic features Translocations involving the MYC oncogene — In virtually all studies, BL is associated with a translocation between the long arm of chromosome 8, the site of the MYC oncogene (8q24), and one of three locations on immunoglobulin (Ig) genes: ⚫ The Ig heavy chain gene on chromosome 14 (approximately 80 percent) – t(8;14) ⚫ The kappa light chain gene on chromosome 2 (approximately 15 percent) – t(2;8) ⚫ The lambda light chain gene on chromosome 22 (approximately 5 percent) – t(8;22) 資料來源： UpToDate Clinical manifestations, pathologic features, and diagnosis of mantle cell lymphoma Epidemiology, clinical manifestations, pathologic features, and diagnosis of Burkitt lymphoma ## Question 169: 一位34歲男士因為皮膚出現紫斑應診，無服藥病史或其他不適。抽血檢查顯示血紅素13.2 gm/dL，血小板12000/μL，白血球數及分類正常，肝、腎功能、尿液及糞便正常。下列何者是對此病人適當的治療？ (1)輸注血小板濃縮液 (2)服用類固醇 (3)脾臟切除 --- - A. (1) - B. (2) - C. (1)+(2) - D. (2)+(3) - E. (1)+(2)+(3) ### Correct Answer: B Approach to the adult with unexplained thrombocytopenia Patients who present with isolated thrombocytopenia and bleeding, manifested by petechiae, purpura, and mucosal bleeding (eg, epistaxis, heavy menstrual bleeding), have a different diagnostic spectrum. ⚫ Individuals with bleeding who lack signs of systemic illness or other abnormalities of the complete blood count are likely to have drug-induced thrombocytopenia or primary ITP. These diagnoses are made based on the appropriate history (eg, drug exposure, bleeding, absence of other specific symptoms) and lack of other findings on physical examination. No additional laboratory testing is needed, with the exception of HIV and HCV testing. ⚫ Individuals with thrombocytopenia and other symptoms have a broader range of potential diagnoses. Specific diagnoses to consider depend on the other clinical findings. As examples: ◼ Fever – Possible infection, sepsis, disseminated intravascular coagulation (DIC) ◼ Hepatosplenomegaly – Possible liver disease with hypersplenism, lymphoma ◼ Neurologic findings – Possible TTP, HUS, DITMA, vitamin B12 deficiency, or copper deficiency ◼ Lymphadenopathy – Possible infection, lymphoma, other malignancy ◼ Thrombosis – Possible HIT, antiphospholipid syndrome (APS), or paroxysmal nocturnal hemoglobinuria (PNH) Immune thrombocytopenia Diagnosis — ITP is a diagnosis of exclusion. It is defined as isolated thrombocytopenia (platelet count <100,000/microL) without anemia or leukopenia and without another apparent cause of the thrombocytopenia. Indications for treatment — The goal of ITP treatment is to provide a safe platelet count to prevent clinically important bleeding, rather than to normalize the platelet count. Clinically important bleeding is often defined as bleeding that requires medical attention. It may range in severity from life-threatening intracerebral hemorrhage to symptoms such as frequent nose bleeds that do not stop with local hemostatic measures, severe menorrhagia that requires hormonal intervention, or oral mucosal blood blisters that may signify greater risk for clinically important bleeding. ⚫ Whom to treat – For all patients with severe bleeding (eg, intracranial, gastrointestinal) and a platelet count <30,000/microL, we recommend immediate platelet transfusion along with ITP-specific therapy with intravenous immune globulin (IVIG) and high-dose glucocorticoids. Platelet transfusions are also appropriate for some patients with higher platelet counts and bleeding in critical sites; early involvement of the consulting hematologist is advised. For all patients with a new diagnosis of ITP and any clinically important bleeding, we recommend ITP-specific therapy, rather than observation, to reduce the risk of worsening bleeding complications. We also suggest ITP-specific therapy for patients with a new diagnosis of ITP and a platelet count <20,000/microL, even in the absence of bleeding symptoms, because the thrombocytopenia may be persistent and become more severe. A platelet count above 20,000/microL provides a margin of safety since severe bleeding typically does not occur unless the platelet count is <10,000/microL. Some patients with platelet count between 20,000 and 30,000/microL may be managed safely with observation and close monitoring. ⚫ Choice of therapy – For patients who require therapy but do not have severe bleeding requiring platelet transfusion, we suggest glucocorticoids rather than IVIG because glucocorticoids are easy to administer, effective, and less costly. Short-term glucocorticoid administration is generally safe and well-tolerated, but high-dose pulse glucocorticoids (eg, high-dose dexamethasone) can be associated with mood alterations and insomnia. IVIG may be used for some patients who do not tolerate glucocorticoid toxicities or added to glucocorticoid treatment for patients who require a more rapid platelet count increase. 資料來源： UpToDate Approach to the adult with unexplained thrombocytopenia Immune thrombocytopenia (ITP) in adults: Clinical manifestations and diagnosis Immune thrombocytopenia (ITP) in adults: Initial treatment and prognosis ## Question 170: 肺腫瘤的治療選項，上皮生長因子接受體(EGFR, epidermal growth factor receptor)的小分子抑制劑藥物是重要的選擇。下列何種病人肺腫瘤有「EGFR突變」的機率最高? --- - A. A 35-year-old woman with a carcinoid tumor - B. A 25-year-old man with a hamartoma - C. A 75-year-old man with squamous cell carcinoma and a history of asbestos exposure - D. A 58-year-old man with a 100-pack-year history of tobacco use with small-cell lung carcinoma - E. A 54-year-old woman who has never smoked with an adenocarcinoma ### Correct Answer: E ->Lung cancer 中以adenocarcinoma 較容易有EGFR mutation,且較容易發生在nonsmoker. Mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase are observed in approximately 15 percent of NSCLC adenocarcinomas in the United States and occur more frequently in nonsmokers . In Asian populations, the incidence of EGFR mutations is substantially higher, up to 62 percent 延伸閱讀：境夫學長補充: 有空可以參考這篇paper: High Frequency of Epidermal Growth Factor Receptor Mutations With Complex Patterns in Non-Small Cell Lung Cancers Related to Gefitinib Responsiveness in Taiwan Paper結論:EGFR mutation易發生在lung adenocarcinoma,族群是年輕(定義是中位數約55歲)、亞洲女性、nonsmoker 資料來源： Uptodate.: Personalized, genotype-directed therapy for advanced non-small cell lung cancer ## Question 171: 一位58歲女性因腳上有一逐漸長大的黑痣而至皮膚科求診，黑痣最長直徑約9mm，邊緣不規則，病人自己發覺黑痣除了逐漸變大之外，顏色也漸加深變黑。切片檢查證實是黑色素瘤(melanoma)，深度由皮膚表面一直延伸入真皮層(dermis)共深達0.5mm，計算每1mm之有絲分裂(mitosis)<1 (<1 mitosis/mm)。下列因素何者對病人黑色素瘤的預後(prognosis)的影響最大? --- - A. Anatomic site - B. Sex - C. Number of mitoses - D. Breslow Depth - E. Clark level ### Correct Answer: D ->影響黑色素瘤預後最重要因子為Breslow thickness：採用“目鏡測微計 ( ocular micrometer ) ”測量腫瘤厚度(侵入厚度)。 The most important prognostic factors for a newly diagnosed patient are incorporated in the staging classification. The best predictor of metastatic risk is Breslow thickness. The anatomic site of the primary is also prognostic; favorable sites are the forearm and leg (excluding the feet), and unfavorable sites include the scalp, hands, feet, and mucous membranes. In general, women with stage I or II disease have better survival than men, perhaps in part because of earlier 延伸閱讀： Breslow thickness is the greatest thickness of a primary cutaneous melanoma measured on the slide from the top of the epidermal granular layer, or from the ulcer base, to the bottom of the tumor ![](https://hackmd.io/_uploads/H1-LywDD2.png) ## Question 172: 一69歲男性，病理切片診斷確診罹患小細胞肺癌 (SCLC, small-cell lung cancer)，PET/CT掃描結果顯示右側肺門(hilar)部位有一4 x 5公分腫塊，且同側有中等量(moderate)的肋膜積水，經肋膜積水穿刺檢查，肋膜積水細胞學證實同樣有SCLC癌細胞。下列敘述何者為真? --- - A. Surgical therapy alone has a high curative rate for his stage of SCLC - B. Radiation plays no palliative role at all in therapy for this disease - C. Twenty percent of patients with SCLC are diagnosed with the same stage of disease as this patient - D. The majority of patients with SCLC of this stage respond to chemotherapy alone and go into remission with a very high 3-year survival - E. This patient has extensive-stage disease ### Correct Answer: E 此病患為T2b : Tumor >4 cm but ≤5 cm in greatest dimension N0 M1a: Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or pericardial nodule(s) or malignant pleural or pericardial effusion◊ TNM:T2bN0M1a: stage 4A A選項: 病患為entensive stage small cell lung cancer 的治療主要是chemotherapy，只有部分limited stage, SCLC(T1 to 2, N0) 可以依靠手術 ---Patients with SCLC rarely survive more than a couple of months without treatment. However, SCLC is highly responsive to multiple chemotherapeutic drugs, and chemotherapy is the mainstay of initial treatment, prolonging survival compared with best supportive care. These benefits may be seen even in patients with advanced disease, poor performance status, and severe organ dysfunction. The addition of immunotherapy to a chemotherapy backbone adds further benefit . B選項: 胸腔的Radiation therapy 在接受過systemic chemotherapy的病人身上，可以改善存活率; 而預防性的brain RT可以減少有症狀的barin meta ---For those with residual disease in the thorax following systemic chemotherapy, thoracic radiation therapy improves survival. Additionally, prophylactic cranial irradiation (PCI) decreases the incidence of symptomatic brain metastases in patients who have responded to systemic chemotherapy, although its impact on overall survival is uncertain. In this modern imaging era, surveillance magnetic resonance imaging (MRI) scans may be considered as an alternative to PCI. C選項: 大部分(66%)SCLC一診斷就是extensive disease --About 2 out of 3 people(66%) with SCLC have extensive disease when their cancer is first found D選項: 病患為extensive disease, survical 為13months, 且<5%能夠活超過兩年。 --The median ranges of survival from the time of diagnosis for limited and extensive disease are 15 to 20 months and 8 to 13 months, respectively. Approximately 20 to 40 percent of limited stage and less than 5 percent of extensive stage patients survive two years . The respective values for five-year survival are 10 to 13, and 1 to 2 percent, respectively E選項: 病患有malignant 的plerual effusion,所以是entensive disease Limited versus extensive stage disease — A modification of the two-stage system originally introduced by the Veterans' Affairs Lung Study Group (VALSG) for use in clinical trials in the late 1950’s continues to be widely utilized in staging patients with SCLC because of its simplicity and clinical utility: ●Limited disease – Tumor confined to the ipsilateral hemithorax and regional nodes able to be included in a single tolerable radiotherapy port (corresponding to Tumor, Node, Metastasis [TNM] stages I through IIIB). ●Extensive disease – Tumor beyond the boundaries of limited disease including distant metastases, malignant pericardial, or pleural effusions, and contralateral supraclavicular and contralateral hilar involvement. 資料來源： 1. uptodate. small cell lung ancer 2. uptodate - Extensive-stage small cell lung cancer: Initial management ## Question 173: 下列危險因子，何者與食道鱗狀上皮細胞癌(squamous cell carcinoma)與食道腺癌(adenocarcinoma)均密切相關? --- - A. Male sex - B. Chronic gastroesophageal reflux disease - C. Barrett's esophagus - D. Lye ingestion - E. Cigarette smoking ### Correct Answer: E ![](https://hackmd.io/_uploads/HyCpkPvv2.png) 資料來源： Harrison,20ed,p566 ## Question 174: 若針對「原發部位不明上皮癌」(CUP, carcinoma of unknown primary)的腫瘤檢體，進行次世代基因定序分析(NGS, next generation sequencing)，最常見發生基因變異(GA, genetic alterations)的基因為下列何者? --- - A. KRAS - B. CDKN2A - C. ARID1A - D. TP53 - E. MTOR ### Correct Answer: D The mean number of GAs was 4.2 per tumor, and the most common GAs included TP53 (55%), KRAS (20%), CDKN2A (19%), and ARID1A (11%). 資料來源： Harrison, 20ed, p660. ROLE OF NEXT GENERATION SEQUENCING ## Question 175: 一位31歲男性，若有下列理學檢查發現或家族病史，會需要將「遺傳性非多發息肉性大腸癌」 (HNPCC，hereditary nonpolyposis colon cancer) 積極列入篩檢(screening)的考慮? --- - A. Innumerable polyps visualized on routine colonoscopy - B. Mucocutaneous pigmentation - C. New diagnosis of ulcerative colitis - D. (A)+(B)+(C) - E. Father, paternal uncle, and paternal cousin with colon cancer diagnosed at age 50, 66, and 35 years, respectively ### Correct Answer: E E選項: 符合三個以上的親屬得到大腸直腸癌; 且其中兩個有一等親屬關係; 一個以上被診斷時年紀小於50歲; 同時兩個世代都有得到大腸直腸癌。 ![](https://hackmd.io/_uploads/ryEVxwwDh.png) Hereditary nonpolyposis colon cancer (HNPCC), also known as Lynch’s syndrome, is another autosomal dominant trait. It is characterized by the presence of three or more relatives with histologically documented colorectal cancer, one of whom is a first-degree relative of the other two; one or more cases of colorectal cancer diagnosed before age 50 in the family; and colorectal cancer involving at least two generations. 資料來源： Harrison, 20ed, p573. Hereditary Nonpolyposis Colon Cancer Uptodate: Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis ## Question 176: 下列病人情形，何者與罹患頭頸部癌症(head and neck cancers)的風險增加，最無關連? --- - A. Alcohol consumption - B. Tobacco consumption - C. Helicobacter pylori infection - D. Epstein Barr virus infection - E. Human papillomavirus infection ### Correct Answer: C A選項 and B 選項: Alcohol and tobacco use are the most significant risk factors for head and neck cancer, and when used together, they act synergistically. Smokeless tobacco is an etiologic agent for oral cancers. Other potential carcinogens include marijuana and occupational exposures such as nickel refining, exposure to textile fibers, and woodworking. D選項: Some head and neck cancers have a viral etiology. Epstein-Barr virus (EBV) infection is frequently associated with nasopharyngeal cancer,especially in endemic areas of the Mediterranean and Far East. EBVantibody titers can be measured to screen high-risk populations and areunder investigation to monitor treatment response. Nasopharyngeal cancer has also been associated with consumption of salted fish and in-door pollution. E選項: In Western countries, the human papilloma virus (HPV) is associated with a rising incidence of tumors arising from the oropharynx, that is, the tonsillar bed and base of tongue. Over 50% of oropharyngeal tumors are caused by HPV in the United States, and in many urban centers this proportion is even higher. HPV 16 is the dominant viral subtype, although HPV 18 and other oncogenic subtypes are seen as well. Alcohol- and tobacco-related cancers, on the other hand, have decreased in incidence. HPV-related oropharyngeal cancer occurs in a younger patient population and is associated with increased numbers of sexual partners and oral sexual practices. 資料來源： Harrison, 20ed, p533. Head and Neck Cancer ## Question 177: 下列何者為最常見的惡性淋巴腫瘤 (lymphoid malignancy)? --- - A. Chronic lymphoid leukemia (CLL) - B. Acute lymphoid leukemia (ALL) - C. Hodgkin lymphoma (HD) - D. Non-Hodgkin lymphoma (NHL) - E. Multiple myeloma (MM) ### Correct Answer: D ![](https://hackmd.io/_uploads/S1-sePPw3.png) ## Question 178: 48歲女性病人，罹患第四期卵巢癌(ovarian cancer)，接受6個療程carboplatin合併paclitaxel化學治療後，比較電腦斷層掃描前後的差異，如療效評估根據Response Evaluation Criteria in Solid Tumors (RECIST), 第1.1版(Ver. 1.1)的定義，若腫瘤治療後可測量的腫瘤「最長直徑」(longest diameters)的總和，共縮小了15%，且效果持續至少4週。可以評估她的卵巢癌對化學治療的"反應" (response)為何? --- - A. Complete response (CR) - B. Partial response (PR) - C. Stable disease (SD) - D. Progressive disease (PD) - E. 以上皆非 ### Correct Answer: C 最長直徑總和需縮小30%以上才可以說Partial Response , PR ![](https://hackmd.io/_uploads/BkgRxvDP2.png) ## Question 179: 有關膽管癌(cholangiocarcinoma)的敘述，下列何者並不正確? --- - A. The incidence of cholangiocarcinoma has been increasing in recent years - B. Primary sclerosing cholangitis and hepatitis C virus infection are associated with cholangiocarcinoma - C. Most patients present due to an abnormal screening ultrasound, without symptoms - D. Asians infected with liver flukes have an increased risk of cholangiocarcinoma - E. Surgical resection may achieve 40% 5-year Survival with an R0 resection ### Correct Answer: C A選項: CCA(cholangiocarcinoma) is the second most common liver cancer following HCC, with a 5-year survival of 10%. iCCA( Intrahepatic cholangiocarcinoma ) has globally increasing incidence and mortality rates. B選項: The classical risk factors for CCA development include primary sclerosing cholangitis (PSC), biliary duct cysts, hepatolithiasis, Carolis disease. -- Common risk factors for HCC, such as HBV and HCV infection and cirrhosis, have been associated to iCCA development. C選項: 因為現行的guideline不會去survery 沒有症狀的病人，因此意外發現的CCA常是因為做其他檢查中發現的，所以被發現的當下大部分是advanced stages -Guidelines are currently not recommending surveillance for early diagnosis, when patients are asymptomatic, since at-risk populations are ill-defined. Cirrhotic patients at risk of HCC development are enrolled in surveillance programs, and can benefit for early detection of iCCA. Otherwise, incidental diagnosis occurs due to crosssectional imaging performed for other reasons. In most cases, iCCA is diagnosed at advanced stages where symptoms such as weight loss, malaise, abdominal discomfort, or jaundice are present. D選項: Parasitic biliary infestation with flukes(血吸蟲) (i.e., most common is Opisthorchis viverrini and Clonorchis sinensis), is a prevalent etiology in Asia that can be prevented with an antihelminth therapy, praziquantel. E選項: ![](https://hackmd.io/_uploads/rk9GWPDwn.png) ## Question 180: 原發部位不明的轉移性上皮癌(carcinoma of unknown primary, CUP)，病理組織常需要額外進行免疫組織染色(immunohistochemical stains)，提供臨床上分辨癌症器官原發來源的參考依據。cytokeratin(CK)是經常使用的intermediate filaments染色，人體有20多種CK亞型，當顯示癌細胞CK20染色陽性且CK7染色陰性(CK20+/ CK7-)時，相對CUP最可能的原發器官為下列何者? --- - A. lung - B. breast - C. endometrium - D. pancreas - E. colon ### Correct Answer: E ![](https://hackmd.io/_uploads/B1iHZDwwh.png) ## Question 181: 12歲男童，被老師發現上課會發呆，課業表現退步，至醫院檢查腦電圖顯示有大腦雙側對稱3 Hz的棘慢複合波（spike-and-slow-wave discharges），關於此疾病的發作時表現下列何者為非? --- - A. 常會眨眼 - B. 有咀嚼動作 - C. 多無倦怠表現 - D. 雙腿無力、跌坐 - E. 過度換氣會誘發 ### Correct Answer: D 3Hz的SWC(Spike-and-wave complex)是典型childhood absence epilepsy (幼童失神性發作)的EEG表現，臨床症狀發作的時候會對外界沒有反應合併automatism (自動症, 會做一些相同無意義的動作例如眨眼[A]咀嚼[B])，發作完之後不會有post-ictal confusion的情況[C]，常見的誘發因子為過度換氣[E] P.S. 會跌坐雙腿無力的癲癇稱為generzlied atonic seizure[D]，可以出現在很多Epilepsy syndrome中，如果合併其他多種癲癇和智力下降則是Lennox Gastaut syndrome (LGS)，EEG表現為1.5~2.5Hz的SWC 資料來源：Bradley's Neurology in Clinical Practice, 7th P.1571, 1576-1577 ## Question 182: 75歲女性，有高血壓、心房顫動病史，平時規則服用dabigatran(110)，突發右側無力與說話不清楚，隨即被送至某一社區醫院急診，美國國家衛生院腦中風量表的分數為7分，腦部斷層掃描顯示無腦內出血，自症狀發生已經120分鐘，應進行下列何處置最適宜? --- - A. 立即給予新鮮冷凍血漿（Fresh frozen plasma, FFP），接續給予靜脈血栓溶解劑 - B. 立即給予凝血?原複合物濃縮物（Prothrombin Complex Concentrate, PCC），接續給予靜脈血栓溶解劑 - C. 立即給予dabigatran反轉劑idarucizumab，接續給予靜脈血栓溶解劑 - D. 立即轉院至可以進行血栓移除的醫院 - E. 先安排斷層掃描血管攝影檢查，再轉院至可以進行血栓移除的醫院 ### Correct Answer: C [A][B][C] 若病患48小時內有使用NOAC不宜直接施打血栓溶解劑，依照歐洲專家建議，如果是dabigatren建議使用反轉藥物idarucizumab再施打血栓溶解劑‧[D][E] 如果使用其他direct thrombin inhibitor，因為無特殊反轉藥物且PCC的效果無法良好評估，因此建議無反轉劑或是使用其他非dabigatren的NOAC接受Brain CTA評估動脈內取栓(IA thrombectomy) P.S. 治療指引指出在疑似或是確診大血管急性缺血腦中風患者，若符合靜脈施打血栓溶解劑條件，可先施打靜脈血栓溶解劑資料來源：2019台灣腦中風學會急性缺血中風靜脈血栓溶解治療指引 P.8-9 ## Question 183: 下列何者較不易有自主周邊神經（autonomic neuropathy）症狀表現? --- - A. 鉛中毒神經病變（lead neuropathy） - B. 糖尿病神經病變（diabetic neuropathy） - C. 澱粉樣神經病變（amyloid neuropathy） - D. 急性間歇性紫質症（acute intermittent porphyria） - E. 肉毒桿菌中毒（botulism） ### Correct Answer: A [只列出大內科會遇到的疾病] 1. 自主神經影響者: AIDP, prophyria [D], amyloid [C], DM [B], paraneoplastic sensory neuronopathy (Anti-Hu) vincristine, 2. 上肢運動神經影響者(類似肌肉病變): prophyria和lead intoxication 3. 會痛的: DM, amyloid, HIV, Fabry, Sjogren syndrome, paclitaxel 4. 本體感覺為主的(走路會搖搖晃晃的): Anti-Hu-related neuropathy, MGUS/MM, Miller-Fisher syndrome, tabes dorsalis (syphilus), CIDP, cisplatin, B6 overdose, Sjogrene syndrome P.S. Tetanus(抑制節前神經元的GABA/Glycine)和Botulism (抑制節前神經元的Ach) [E] 兩者都是神經肌肉交界疾病，都會有ANS involvement 資料來源：Bradley's Neurology in Clinical Practice, 7th P.1796-1798 ## Question 184: 22歲女性，近3個月有漸進的易怒、精神不集中、記憶力下降、睡眠障礙，甚至有妄想症狀，至精神科就診，突發癲癇被送至急診，初步診斷為非感染性腦炎，應優先考慮安排哪些檢查：(1)心臟超音波 (2)腹部骨盆腔斷層掃描 (3)凝血相關血液檢查 (4) 免疫相關血液檢查。 --- - A. (1)+(3) - B. (2)+(4) - C. (1)+(4) - D. (2)+(3) - E. (1)+(2)+(3)+(4) ### Correct Answer: B 精神症狀合併快速進展失智，而後發生癲癇以及動作障礙異常，需要考慮Limbic encephalitis：年紀大的需考慮Anti-GABA-A/B or Anti-AMPA, related to small cell lung cancer；年紀輕的女性需考慮Anti-NMDA encephalitis, related to “ovarian teratoma”‧Anti-NMDA encephalitis的疾病是有順序進程的包含：(1)精神症狀(psychiatric symptoms), (2)記憶力異常(memory deficits), (3)癲癇(seizures, EEG: delta brush), (4) 意識改變(decreased level of consciousness), (5) 臉部不自主運動 (orolingual dyskinesia)以及(6)自主神經功能異常(autonomic disturbances)。檢查主要是用Brain MRI確定Limbic involvement和CSF排除HSV或是其他病毒腦炎，同時可以測定Blood/CSF中Anti-NMDA antibody作為確認診斷。治療可用steroid pulse therapy, IVIg, plasmapheresis, anti-CD20 therapy (rituximab)及切除腫瘤資料來源：Bradley's Neurology in Clinical Practice, 7th P.1196-1198 ## Question 185: 下列哪一部位的腦梗塞較不常是心因性腦梗塞發生位置? --- - A. 枕葉（occipital lobe） - B. 小腦外側（lateral cerebellum） - C. 雙測視丘（bilateral thalamus） - D. 頂葉皮質部（parietal lobe cortex） - E. 橋腦近中側（medial pons） ### Correct Answer: E 心因性梗塞比較容易影響大血管末端而比較不容易影響penetrating artery。Occipital lobe = PCA, Lateral cerebellum = PICA, “B”ilateral thalamus = BA, Parietal lobe = MCA, inferior branch，腦幹均為penetrating artery所支配的(即lacunar infarction常見位置: putamen, pons ,posterior limb of the internal capsule, caudate and “u”nilateral thalamus) 資料來源：Bradley's Neurology in Clinical Practice, 7th P.933 ## Question 186: 50歲男性，近一個月幾乎每日頭痛，痛在顳葉、眼後部位，每次頭的時間約1-2小時，痛時候合併有鼻塞、流眼淚症狀，2年前有類似症狀持續1-2個月，請問下列哪一個藥物不會選擇為預防頭痛發作藥物? --- - A. Verapamil - B. Gabapentin - C. Indomethacin - D. Topiramate - E. Lithium ### Correct Answer: C 頭痛在“單側”顳葉/眼窩合併自主神經症狀(鼻塞眼紅流眼淚)屬於TAC(Trigeminal autonomic cephalagia)，依照發作時間可以分為Hemicrania continua(20mins~several days) [最長, 天], Cluster headache(15min~180mins) [長, 時], Proxysmal hemicrania(2~30mins) [中, 分], SUNA/SUNCT(5secs-240secs) [最短, 秒]，對於Paroxysmal hemicrania和Hemicarnia continua女性比較多而其他兩者則是男性取向. 急性用藥包含Oxygen, Triptan, Ergotamine；慢性用藥包含CCB(Verapamil)[A], Lithium[E], Valproate, Topiramate[D] 和 steroid P.S. Indomethacin-responsive headache: Valsalva-related headache, Hemicrania continua, Paroxysmal hemicrania, SUNCT and Stabbing headaches P.S. 目前Gabapentin在Cluster headache治療上證據力不足(有文章但不多) 資料來源： Bradley's Neurology in Clinical Practice, 7th P.1708 ## Question 187: 關於高沙可夫症候群（Korsakoff's syndrome）下列敘述何者正確? --- - A. 與基底核(basal ganglia)受影響相關 - B. 最主要症狀為嚴重記憶缺損 - C. 之前不會出現有韋尼克氏腦病變(Wernicke encephalopathy)症狀 - D. 經維他命B1治療，大多數可以明顯恢復 - E. MRI可見間腦(Diencephalon)萎縮 ### Correct Answer: D Wernicke-Korsakoffs syndrome為一個維生素B1缺乏症候群，在長期酗酒或是接受外科開刀使用TPN者容易發生，Wernicke encephalopathy為三聯合症狀(步態不穩, 意識改變, 眼外肌移動異常)，核磁共振會出現Hyperintensity (T2WI/DWI) in (1) mammillary body, (2) tectum of midbrain, (3) bilateral medial thalamus [diencephalon] and (4) fronto-parietal cortex；Korsakoff encephalopathy為反覆Wernicke encephalopathy留下的後遺症，主要是anterograde and retrograde amnesia，因而造成confabulation的情況產生，MRI主要是Brain atrophy (剛才提及的地方萎縮)表現‧及時使用針劑B1治療Wernicke encephalopathy很有效，數小時或是數天之後症狀會改善，但是一旦變成Korsakoff syndrome則治療效果並不明顯 P.S. 我覺得答案怪怪的, (B)/(E)好像都可以 (A)為丘腦和中腦, (B)我覺的是對的, (C)他就是WE的後遺症, (D)大多數是不可逆的, (E)病理解剖上發現Thalamus (Diencephalon)萎縮最嚴重資料來源： Bradley's Neurology in Clinical Practice, 7th P.1232-1233 Adams and Victor's Principles of Neurology, 10th P.1162-1166 ## Question 188: 關於親密關係暴力(intimate partner violence)與臨床醫學的關聯性，下列何者為非？ --- - A. 暴露於親密關係暴力，會增加罹患氣喘、中風或心血管疾病的風險 - B. 個案有經常性的頭頸顏面的骨折或撕裂傷，也需要考慮親密關係暴力的可能性 - C. 親密關係暴力也可以透過限制受害伴侶的求醫行為來呈現，導致受害伴侶醫療配合度(medical adherence )不佳 - D. 協助患者揭露親密關係暴力經驗，不需要在隱密安全的情境下詢問，而且首次見面就可以問得出來 - E. 熟悉並提供轉介資源，如113專線或各縣市家庭暴力與性侵害防治中心聯絡方式，有助於防範親密關係暴力 ### Correct Answer: D 出自NEJM的一篇文章(1) （A）： ![](https://hackmd.io/_uploads/H1DYGwPv2.png) （B）Particular physical injuries in women are recognized indicators of intimate partner violence. These include contusions, lacerations, and fractures, especially in the head, neck, and face.(1, 2) （C）Subtle aspects of psychological aggression include interference with a person’s attempts to seek medical care, keep appointments, obtain medications, adhere to treatment recommendations, or improve health behaviors, potentially making the person who is experiencing such controlling behavior appear to be medically nonadherent.(1) （D）Qualitative studies indicate that women experiencing such violence want health care providers to talk to them about the violence in a safe and private setting, to be prepared to ask multiple times without pushing for disclosure, and to offer tangible medical and social resources for support.(1) （E）It has been suggested that universal education about prevention and counseling about harm reduction in relation to intimate partner violence shifts the emphasis away from disclosure-driven practices and counteracts the assumption that a “no” response to a screening question about partner violence means that the patient has not experienced violent or controlling behavior.(1) ## Question 189: 關於重度憂鬱症(major depression)的病因學下列何者為非？ --- - A. 雙胞胎研究呈現中等程度的遺傳率 (moderate heritability) - B. 海馬迴體積(hippocampal volume)減少是在大腦結構上一致的發現 - C. 在功能性腦造影研究常發現杏仁核(amygdala)活性增加 - D. 近年全基因組關聯性分析(GWAS)已經找到大量可重複驗證的致病基因位點 - E. 近年研究發現發炎反應也與重度憂鬱症病因相關 ### Correct Answer: D 此題出自NEJM和Lancet。(3, 4) （A） heritability： 37%。(3) （B） Elevated levels of glucocorticoids can reduce neurogenesis, and this has been suggested as a mechanism for the decreased size of the hippocampus on magnetic resonance images of the brain in many patients with depression.(3) （C） Converging findings from these studies suggest abnormally increased amygdala, ventral striatal, and medial prefrontal cortex activity, mostly to negative emotional stimuli, such as fearful faces. (4) （D） Genetic, molecular, and neuroimaging studies continue to contribute to advances in our understanding of the neurobiological basis of major depressive disorder. However, the extent to which findings from neurobiological studies can help improve the clinical and functional outcome of individuals with the disorder is still uncertain.(4) （E） Signs of inflammatory processes have been described in major depression.(3) ## Question 190: 關於憂鬱症的心理治療下列何者為非？ --- - A. 在憂鬱症的心理治療中，認知行為治療(CBT)以及人際關係治療(IPT)是兩種常見的治療模式 - B. 對於病情較嚴重的憂鬱症患者，病人難以投入(engage)心理治療過程，故僅使用心理治療的療效不佳 - C. 目前學界可以清楚區分不同心理治療模式療效的差異所在 - D. 對於比較輕的憂鬱症，心理治療與藥物治療的效果類似 - E. 不同心理治療模式共同的療效關鍵不外乎讓個案感到溫暖、正向、以及真誠的照顧 ### Correct Answer: C 此題出自NEJM(5) （A）The data provide support for cognitive behavioral therapy, interpersonal therapy, and behavioral activation as first-line treatments for mild-to-moderate depression.(5) （B）Antidepressant drugs have been shown to have a favorable benefit–risk profile in moderate-to-severe depression. Psychotherapy may also be a first-line choice for moderate depression.(5) VS意見：重鬱症之症狀，包括無動力、注意力障礙、無活力等，會干擾心理治療的進行。（C）No significant differences were noted among various types of psychotherapy, including — but not limited to — cognitive behavioral therapy (identifying and modifying negative thoughts that adversely affect emotion and behavior), behavioral activation (scheduling positive activities and increasing positive interactions), and interpersonal psychotherapy (addressing interpersonal issues in a highly structured manner).(5) （D）For mild depression, initial preference should be given to psychotherapy and symptom monitoring, with pharmacotherapy reserved for cases of insufficient improvement. Psychotherapy, pharmacotherapy, or both should be considered for moderate depression.(5) VS意見： 1. 輕度：心理治療 2. 中度：藥物治療及（或）心理治療 3. 重度：藥物治療及（或）其他生物療法（例如：electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS)）（E）VS意見：此為所有醫療的必備條件！！！ ## Question 191: 關於憂鬱症的生物性治療下列何者為非？ --- - A. 選擇性血清素再吸收抑制劑(SSRI)常見的副作用可能包括性功能障礙、噁心、頭痛、體重上升 - B. 大約有三分之一的病患，可以藉由醫師處方的第一種抗憂鬱藥獲得痊癒(full remission) - C. 曾有國外大型階段性藥物試驗研究結果呈現，在嘗試了四種不同的抗憂鬱藥物後，累積起來也只有二分之一的病患獲得痊癒 - D. 為了因應單一線抗憂鬱藥物療效不彰的問題，有時候得嘗試augmentation，例如抗憂鬱藥物合併lithium或是部分atypical antipsychotics - E. 多重藥物治療反應不佳或是自殺風險較高的患者，可以考慮電氣痙攣治療法(ECT) ### Correct Answer: C 可參考NEJM於2019的文章。(5) （A） ![](https://hackmd.io/_uploads/Hy_GXvDD2.png) ![](https://hackmd.io/_uploads/ByKmXvDw3.png) （B）依據重鬱症治療中，最重要的臨床試驗STAR*D：(5) Level 1 (第一種抗憂鬱藥物治療)：response rate (47%)，remission rate (37%)。（C）同前，經Level 1~4 （共四步驟，包含藥物治療及心理治療），cumulative remission rate （67%）。（D）Augmentation意指加入一種Non-antidepressant medication來增強原有antidepressant medication的療效。 Second-line: Antidepressant + atypical antipsychotics (e.g., quetiapine, aripiprazole, olanzapine, etc.) Third-line: Antidepressant + lithium carbonate (E) Briefly, the primary indications for ECT among patients with depression are lack of a response to or intolerance of antidepressant medications, a good response to previous ECT, and the need for a rapid and definitive response (e.g., because of psychosis or a risk of suicide). ECT can be used in both unipolar and bipolar disorders.(6) ## Question 192: 關於廣義的精神病(psychotic disorders)類群各種疾患的終生盛行率(lifetime prevalence)，下列何者為非？ --- - A. 思覺失調症(schizophrenia)：0.30%-0.87% - B. 帶有精神病特徵的雙極情感疾患(bipolar disorder with psychotic feature)：0.12% - C. 帶有精神病特徵的重度憂鬱症(major depressive disorder with psychotic feature):：0.33% - D. 妄想症(delusional disorder)：0.18% - E. 產後精神病(postpartum psychosis)：7% ### Correct Answer: E Lifetime prevalence of psychotic and bipolar I disorders in a general population. The lifetime prevalence of all psychotic disorders was 3.06% and rose to 3.48% when register diagnoses of the nonresponder group were included. Lifetime prevalences were as follows: 0.87% for schizophrenia, 0.32% for schizoaffective disorder, 0.07% for schizophreniform disorder, 0.18% for delusional disorder, 0.24% for bipolar I disorder, 0.35% for major depressive disorder with psychotic features, 0.42% for substance-induced psychotic disorders, and 0.21% for psychotic disorders due to a general medical condition. The National Hospital Discharge Register was the most reliable of the screens (kappa = 0.80). Case notes supplementing the interviews were essential for specific diagnoses of psychotic disorders. (E) 0.1%~0.2%. Postpartum psychosis is relatively rare, occurring in 1 to 2 per 1000 births, and is far less common than postpartum blues and postpartum depression. A 2017 systematic review found low incidence rates ranging from 0.89 to 2.6 per 1000 women. Multiple studies have shown the relative risk (RR) of a hospital admission for psychosis to be increased during the first month postpartum (RR 1.09 to 21.7) compared with any other time in a woman's life 資料來源： Uptodate Arch Gen Psychiatry. 2007;64(1):19-28. doi:10.1001/archpsyc.64.1.19 ## Question 193: 關於思覺失調症(schizophrenia)的心理治療，下列何者為非？ --- - A. 目前學界支持單純以心理治療方式治療思覺失調症 - B. 認知行為治療(CBT)被證實可以減輕患者來自幻聽或妄想的痛苦 - C. 家族精神衛教(family psychoeducation)有助於家族成員支持病患走向重建之路 - D. 社交技巧訓練(social skill training)適合症狀嚴重的急性期病患 - E. 針對會引發精神病症狀的刺激，施以嚴謹的行為暴露治療(behavioral exposure)，有助於建立現實考驗感(reality testing) ### Correct Answer: A （A）At present, treatment mainly consists of antipsychotic drugs combined with psychological therapies, social support, and rehabilitation.(7) (B)~(E)參考下表：(8) ![](https://hackmd.io/_uploads/HJ4YXvPw2.png) ## Question 194: 下列哪幾個藥物有獲得美國FDA治療酒精使用疾患(alcohol use disorder)的許可證？(1)Vareniciline (2)Naltrexone (3)Disulfiram (4)Baclofen (5)Acamprosate --- - A. (1)+(2)+(3) - B. (1)+(3)+(5) - C. (2)+(3)+(4) - D. (2)+(3)+(5) - E. (3)+(4)+(5) ### Correct Answer: D 目前僅有Naltreaxone、Disulfiram、Acamprosate，有獲得美國FDA治療酒精使用疾患(alcohol use disorder)的許可，長庚都有噢！ (1)Vareniciline: 戒菸口服藥物 ## Question 195: 關於疥瘡(scabies)以下何者錯誤? (1)感染人類之疥蟲(Sarcoptes scabei var. hominis)生命周期約 30 天；(2)疥蟲離開人體皮膚最多可存活 3 天；(3)抗疥藥膏局部厚塗於患部就可徹底殺疥蟲；(4)如確定感染，家中寵物(如貓狗)也須一併治療；(5)成人好發於手臂、腿部、背部及臉部 --- - A. (1)+(2)+(3) - B. (2)+(3)+(4) - C. (1)+(3) - D. (2)+(4) - E. (3)+(4)+(5) ### Correct Answer: E A. The life cycle of mites is completed entirely on human skin. The female mite, by a combination of chewing and body motions, is able to excavate a sloping burrow of 0.5 to 5 mm/day in the stratum corneum to the boundary of the stratum granulosum.7,8 Along this path, which can be 1 cm long, she lays anywhere from 0 to 4 eggs a day, or up to 50 eggs during her life span of 30 days. Eggs hatch in 10 to 12 days and larvae leave the burrow to mature on the skin surface. After the larvae molt, they become nymphs which can only survive 2 to 5 days off host. The male mite lives on the surface of the skin and enters burrows to procreate. => (1)正確 B. The scabies mite is able to live for 3 days away from the host in a sterile test tube, and for 7 days if placed in mineral oil mounts.4,6 Mites cannot fly or jump. => (2)正確 C. Scabies is treated by a combination of a scabicide and fomite control. Topical scabicides are applied overnight to the entire skin surface with special attention to finger and toe creases, cleft of the buttocks, belly button, and beneath the fingernails and toenails. In adults, one can exclude treating the scalp and face. => 頸部以下全身都要塗抹藥膏，非局部，故(3)錯誤 D. Scabies is an infestation by the highly host-specific mite, Sarcoptes scabiei var. homini, family Sarcoptidae, class Arachnida. Because of the common occurrence of asymptomatic mite carriers in the household, all family members and close contacts should be treated simultaneously. => (4)錯誤 E. Patients display excoriations and eczematous dermatitis that favors the interdigital webs, sides of fingers, volar aspects of the wrists and lateral palms, elbows, axillae, scrotum, penis, labia, and areolae in women. The head and neck are usually spared in healthy adults, but in infants, elderly, and immunocompromised individuals, all skin surfaces are susceptible. => 疥蟲在一般成人不太會感染頭頸部，只有嬰兒、老人、免疫力不全的人疥蟲才會跑到頭頸部，挪威疥例外(一般成人頭頸部也會有lesion)，故(5)錯誤資料來源： Fitzpatrick’s Dermatology 9th Edition, Chap.178, Page 3274-3276 ## Question 196: 非瘢痕型落髮(nonscarring alopecia)可能之原因? (1)Alopecia areata；(2)Syphilis；(3)Androgenetic alopecia；(4)Discoid lupus erythematosus；(5)Lichen planopilaris --- - A. (1)+(2)+(3) - B. (2)+(3)+(4) - C. (1)+(3) - D. (2)+(4) - E. (3)+(4)+(5) ### Correct Answer: A ![](https://hackmd.io/_uploads/SJODVDDv3.png) → (D)(E) 的Discoid lupus erythematosus 和 Lichen planopilaris 是造成scarring alopecia的原因資料來源： Harrison 20th Edition, Part 2, Chap.54, Page 341 ## Question 197: 下列關於蕁麻疹(urticaria)之敘述，何者為非？ --- - A. 常用抗組織胺藥物治療 - B. 所有的病人皆可找出原因 - C. 併用aspirin，常使此病惡化 - D. 蕁麻疹之單一病灶常在24小時內消失 - E. 應先詢問病人的用藥史 ### Correct Answer: B A. For most forms of urticaria, H1 antihistamines such as chlorpheniramine or diphenhydramine effectively attenuate both urtication and pruritus, but because of their side effects and short half-life, long-acting, non-sedating agents such as loratadine, desloratadine, and fexofenadine, or low-sedating agents such as cetirizine or levocetirizine generally are used first and increased to four times daily (QID) dosing. B. Chronic urticaria is often idiopathic. C. NSAIDs worsen symptoms in 25 to 50 percent of patients with chronic spontaneous urticaria. D. Urticarial lesions last for <24 h, frequently migrate around the body, leave no bruising or scarring and are intensely pruritic. E. Acute urticaria is most often the result of exposure to a food, environmental or drug allergen or viral infection. 延伸閱讀： ![](https://hackmd.io/_uploads/HkxjEDwwn.png) 資料來源： Harrison 20th Edition, Part 11, Chap.345, Page 2500-2503 Uptodate – Chronic spontaneous urticaria: Clinical manifestations, diagnosis, pathogenesis, and natural history ## Question 198: 一位實習醫師突然在臉部及軀幹發生如圖示的皮疹，併有發燒，最可能的診斷是？ ![](https://hackmd.io/_uploads/HkDCEvDDn.png) --- - A. Varicella B. Stevens-Johnson syndrome C. Rubella D. Sudamina E. Pityriasis lichenoides et varioliformis acuta ### Correct Answer: A A. Varicella (chickenpox) and herpes zoster (shingles) are distinct clinical entities caused by a single member of the herpesvirus family, varicella-zoster virus (VZV). Varicella, a highly contagious exanthem that occurs most often in childhood, is the result of primary VZV infection of a susceptible individual. The rash of varicella usually begins on the face and scalp and spreads rapidly to the trunk, with relative sparing of the extremities. Lesions are scattered, rather than clustered, reflecting viremic spread to the skin, and they progress sequentially from rose-colored macules to papules, vesicles, pustules, and crusts. Lesions in all stages are usually present at the same time. (A dew drop on a rose pedal 玫瑰花瓣上的露珠)=> 皮疹集中在臉部及軀幹，且皮疹合併有小水泡(vesicles) B. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are acute life-threatening mucocutaneous reactions characterized by extensive necrosis and detachment of the epidermis and mucosal epithelium. The exact pathophysiology of epidermal necrolysis (EN) is still unclear; however, drugs are the most important etiologic factors. => SJS通常是藥物引起，不會突然得到 ![](https://hackmd.io/_uploads/r1JlBDDD3.png) C. Rubella also called German measles and 3-day measles. Skin rash duration of 2 to 3 days, with enlargement of cervical, suboccipital, and postauricular glands. High risk of fetal malformations with congenital infection (microcephaly, congenital heart disease, and deafness), particularly in the first trimester. The exanthem, occurring 14 to 17 days after exposure, is characterized by pruritic pink to red macules and papules that begin on the face, quickly progressing to involve neck, trunk, and extremities. Lesions on the trunk may coalesce, whereas those on the extremities often remain more discrete. The rash usually begins to disappear in 2 to 3 days, unlike rubeola, which can be more persistent and clears the head and neck first. Desquamation may follow resolution of the rash. => Rubella出生後都會接種疫苗，成年實習醫師基本上不會得到，且通常會合併耳後淋巴結腫大 ![](https://hackmd.io/_uploads/HygWBDPDn.png) D. Sudamina這名詞很少用，其實就是miliaria crystallina。Miliaria results from obstruction of eccrine sweat ducts and occurs in conditions of increased heat and humidity. There are three types of clinically distinctive miliaria classified based on the level of the obstruction: miliaria crystallina, miliaria rubra, and miliaria profunda. In miliaria crystallina, ductal obstruction occurs at the stratum corneum. It presents as small, 1-mm, clear, fragile, vesicles that rupture easily. They are commonly seen on the face and upper trunk in infants and on the trunk in adults. ![](https://hackmd.io/_uploads/HJXGBPvw3.png) E. Pityriasis lichenoides et varioliformis acuta (PLEVA) manifests as recurrent crops of erythematous papules that develop crusts, vesicles, pustules, or erosions before spontaneously regressing within a matter of weeks. ![](https://hackmd.io/_uploads/H1vmBDvD2.png) 資料來源：Fitzpatrick’s Dermatology 9th Edition ## Question 199: 30歲男性, 皮膚病變如圖, 以下何者為必需之處置？(1) 抽血檢查有無HIV感染； (2) 詢問性行為史；(3) 抽血檢查有無梅毒；(4) 切取組織作病理檢查 ![](https://hackmd.io/_uploads/SyyISwDP3.png) --- - A. (1)+(3) - B. (2)+(4) - C. (1)+(2)+(3) - D. (4) - E. (1)+(2)+(3)+(4) ### Correct Answer: C 看起來是肛門處且像是菜花，應一併檢查有無其他性病史 General appearance of warts • lesions characterized by o solitary keratotic papule or plaque (initially) o small, nondistinctive 1-2 mm flesh-colored papules (may retain this presentation for duration of infection) o more frequently found in large clusters on external genitalia o may grow as large as several inches in diameter • highly variable appearance o color may range from white to pink, purple, red, or brown o appearance may range from flat to cerebriform or verrucous o can be dome-shaped, cauliflower-shaped mass, or pedunculated Diagnosis • (4)Patients who present with typical appearing condyloma acuminata do not need a vulvar biopsy. If clinical doubt about the diagnosis exists, perform a biopsy. Making the diagnosis • diagnosis usually made by visual inspection of characteristic skin lesions during clinical exam • diagnosis can be confirmed by biopsy but this is seldom needed to diagnose visible genital warts • detection and typing of human papillomavirus (HPV) not currently recommended for diagnosis or management of external genital warts • mild acetic acid not routinely recommended for diagnosis but might improve wart visualization in mild or subclinical cases • both partners usually infected if in ongoing sexual relationship, although signs may not be apparent in both partners 資料來源：Condyloma Acuminatum- Dynameds ## Question 200: 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： ![](https://hackmd.io/_uploads/S1K2HPwvn.png) --- - A. Systemic lupus erythematosus - B. Solar dermatitis - C. Rosacea - D. Dermatomyositis - E. Ofuji disease ### Correct Answer: C A. The most common lesion is a facial eruption that characterizes acute cutaneous lupus erythema (also known as "the butterfly rash") that presents as erythema in a malar distribution over the cheeks and nose (but sparing the nasolabial folds病患看起來有involve到此處) that appears after sun exposure B. Solar urticaria is a rare variant of urticaria. Pruritic, erythematous wheals appear within 5 to 10 minutes of sun exposure and resolve within 24 hours. Symptoms can be induced via exposure to UVA, UVB, or visible light; the precise wavelengths vary from individual to individual ![](https://hackmd.io/_uploads/Sky1IDDP3.png) C. 酒槽或酒槽鼻findings may include • flushing • erythema and telangiectasias over cheeks and forehead • edema of skin • papules and pustules over nose, forehead, and cheeks D. rash may present as 1 characteristic sign or combination of signs, including 1. Gottron's sign is erythematous to violaceous macules over extensor surfaces of joints, typically below knee ![](https://hackmd.io/_uploads/BybxIDDPn.png) ![](https://hackmd.io/_uploads/B1ZZUvDP2.png) ![](https://hackmd.io/_uploads/SkC-LwDP3.png) 5. rash may be photosensitive with poikiloderma ![](https://hackmd.io/_uploads/HkLmUDww2.png) E. Ofuji disease (Eosinophilic pustular folliculitis) 又名嗜伊紅性膿皰性毛囊炎(eosinophilic pustular folliculitis). 臨床可見於耳前，臉頰，反覆發作的環狀紅色斑塊，斑塊週邊可見膿皰參雜。通常伴隨強烈搔癢感，病因未明，好發於亞洲人。病理切片可見典型嗜伊紅性血球於毛囊及毛囊週圍發炎浸潤。治療方面，Indomethacin,prednisolone,dapsone等皆有效。 ![](https://hackmd.io/_uploads/SJLrUDvwh.png) ## Question 201: 如圖所示臉部的慢性增大單一腫塊，下列何者是最可能的診斷？ ![](https://hackmd.io/_uploads/BkFF8wPDh.png) --- - A. Basal cell carcinoma - B. Melanoma - C. Seborrheic keratosis - D. Sebaceous carcinoma - E. Squamous cell carcinoma ### Correct Answer: A A. Superficial type— Approximately 15 percent of BCCs are superficial BCCs. For unclear reasons, men have a higher incidence of superficial BCC than do women. Superficial BCCs most commonly occur on the trunk and typically present as slightly scaly, non-firm macules, patches, or thin plaques light red to pink in color . The center of the lesion sometimes exhibits an atrophic appearance and the periphery may be rimmed with fine translucent papules. A shiny quality may be evident when a superficial BCC is illuminated. Occasionally, spotty brown or black pigment is present, which may contribute to confusion with melanoma. Superficial BCCs tend to grow slowly, and can vary in size from macules measuring just a few millimeters in diameter to lesions several centimeters in diameter or more if left untreated. Superficial BCCs are usually asymptomatic. ![](https://hackmd.io/_uploads/BkN3IPDD2.png) ![](https://hackmd.io/_uploads/Bk4T8vvD3.png) ![](https://hackmd.io/_uploads/ryx0LvwDh.png) ![](https://hackmd.io/_uploads/HkACIPDwh.png)