義大醫院兒童醫學部 1 目錄 1 Orientation 2 兒科病房常用藥物 4 兒童心臟科 12 兒童內分泌 30

兒童過敏免疫風濕科

1. 
   過敏性休克反應(Anaphylactic Reactions)
   

1. 
   General concepts
   

1. 
   Life-threatening.
   
2. 
   Can occur with extreme rapidity and immediate treatment is critical.
   
3. 
   Death is most commonly from asphyxia (airway obstruction) and/or cardiovascular collapse (anaphylactic shock).
   
4. 
   Signs and symptoms include pallor, weakness, pruritus, erythema, urticaria, dyspnea, wheezing, cyanosis, nausea, vomiting, diarrhea, abdominal cramps, palpitations, cardiac arrhythmias, frothy sputum with pulmonary edema, hypotension, and localized or generalized edema.
   
5. 
   With edema of the upper airway, the patient may complain of a "thick" throat before any respiratory impairment is perceived. On the other hand, the reaction may produce cardiovascular collapse so rapidly that there are no warning symptoms or signs.
   

1. 
   Etiology
   Severe anaphylactic reactions are often caused by
   

1. 
   
   
   1. 
      
      
   2. 
      
      
      1. 
         Injection of drugs (especially penicillin)
         
      2. 
         Biologics (foreign serum, intravenous immune globulin)
         
      3. 
         Hyposensitization therapy with allergenic extracts
         
      4. 
         Skin test
         
      5. 
         Ingestion of food allergens (especially fish, milk, peanuts, other nuts, and shellfish)
         
      6. 
         Insect stings
         
      7. 
         Radiocontrast media
         
   3. 
      Diagnosis
      An association between substances eaten, inhaled, injected, or touched and the symptoms observed should be regarded as highly suggestive and a causal relationship assumed until the relationship can be investigated. Skin testing with suspected allergens is sometimes useful, but it should be performed with caution, beginning with extremely low concentrations of the suspected allergens. In the case of drugs or foreign sera, for example, it is advisable to begin with at least a thousandfold dilution of the material and to start with a scratch or prick test rather than an intradermal test. As soon as an obvious reaction occurs, the allergen should be wiped from the skin. When skin tests are used to identify the cause of a severe allergic reaction, it must be remembered that a positive skin reaction may occur without severe hypersensitivity and that a negative skin reaction does not completely exclude the possibility that the material in question plays a role in the reaction investigated.
      

1. 
   If the testing material is in a form different from that which provoked the reaction in the first place (some foods and antibiotics).
   
2. 
   If testing is performed too soon after the reaction during a transient anergic period ("refractory period").
   
3. 
   If testing is performed too long after the original reaction (years or possibly months), so that the level of IgE antibody has waned. The latter occurs frequently in penicillin hypersensitivity.
   
4. 
   If anaphylaxis is caused by non-IgE antibody such as immune complex or complement-mediated agents, by modulators of arachidonic acid metabolism, or by direct histamine-releasing agents.Because of the possible occurrence of a refractory period, testing should be deferred for 1 month after a systemic reaction.
   
1. 
   Treatment
   Treatment of severe allergic reactions begins with the immediate intramuscular injection of 0.2 to 0.5 ml (0.01 ml/kg) of 1:1000 aqueous epinephrine. This may be repeated at 20-minute intervals if necessary. If the material that provoked the reaction was injected into an extremity, a tourniquet should be placed proximal to the site of injection to retard absorption. If the material was injected intradermally or subcutaneously, infiltration of the injection site with 0.2 ml of aqueous epinephrine and application of ice may slow absorption. Diphenhydramine (Benadryl), 1 mg/kg up to 50 mg, should be given intravenously, slowly over a 5- to l0-minute period, or intramuscularly. An H2 antihistamine, cimetidine (300 mg), should be infused intravenously over a 5- to l0-minute period as well. Parenteral or oral antihistamines may be repeated every 4 to 6 hours as necessary.
   
   Oxygen by mask should be administered while an intravenous infusion of 5% dextrose in water is started to provide a route for subsequent fluid, colloid, or drug therapy. An adequate airway should be ensured. An intubation and tracheostomy set should be available nearby, and appropriate surgical or anesthesiology personnel should be notified. In addition to fluids, plasma may be required to maintain an appropriate blood volume. Maintenance of adequate blood pressure may require presser agents. A cardiac monitor should be in place, because anaphylaxis may lead to decreased coronary blood flow.

   The value of adrenal steroids in acute severe allergic reactions is unclear, because the onset of their therapeutic effects requires several hours. However, in acute reactions not immediately responsive to epinephrine and antihistamine therapy, they should be given. Methylprednisolone or equivalent given intravenously in large doses (1 to 2 mg/kg body weight every 6 hours) is recommended. After symptoms diminish, adequate control can be maintained with oral antihistamines alone or in combination with ephedrine. Late complications of anaphylaxis include occlusion of the airway, hypotension, cardiac arrhythmias, hypoxic seizures, and metabolic acidosis. For therapy of these conditions a hospital intensive care unit and blood gas laboratory are essential.

   
   
2. 
   Prevention
   Subsequent avoidance of the inciting allergens is imperative. Sensitive individuals should be told of possible hidden sources of allergens. Individuals sensitive to an antibiotic should be warned against the subsequent use of a structurally related antibiotic. In severe insect hypersensitivity, hyposensitization should be instituted, preferably by a physician with experience in hyposensitization therapy. In children, hyposensitization is indicated if a reaction has involved respiratory or cardiovascular symptoms, but otherwise it may not be warranted. Immunizations should be kept up to date in order to minimize the necessity for using foreign antisera.
   

2.1 氣喘的定義

2.2 氣喘病人的肺功能異常

主要有二種：氣道過度反應和急性氣流阻礙。

2.2.1氣道過度反應(bronchial hyperresponsiveness)

2.2.2 氣喘的反覆性氣流阻滯可以由於下列四種變化：

• 
  急性支氣管收縮：急性支氣管收縮主要是經由IgE-的作用誘發出許多物質，包括由氣道肥大細胞製造的組織胺、前列腺素(prostaglandin)和白三烯(leukotriene)引起平滑肌的收縮。此種反應，稱為早期的氣喘反應。
  
• 
  氣道壁的腫脹：氣流阻滯可能是單獨的氣道壁水腫或合併平滑肌的收縮而造成。此一氣喘反應是一種發炎反應，可在6到24小時後出現，稱為晚期的氣喘反應。
  
• 
  慢性的黏液栓塞：主要是因為黏液分泌及滲出的血清蛋白及細胞碎片堵住細小的支氣管。
  
• 
  氣道壁的變形：這是因為長期及嚴重的氣喘導致氣道間質的結構性變化。
  

1. 
   
   
2. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
      1. 
         曾有喘鳴或反覆出現喘鳴。
         
      2. 
         曾有明顯之夜間咳嗽。
         
      3. 
         曾經在運動後，出現咳嗽或喘鳴。
         
      4. 
         當吸入污染空氣會有咳嗽、胸悶或喘鳴。
         
      5. 
         一有感冒即感胸悶。
         
      6. 
         每當接觸有毛動物或花粉即感胸悶或喘鳴。
         
      7. 
         服用阿司匹林或乙型交感神經阻斷劑即感胸悶或喘鳴。
         

2.5 氣喘病之肺功能試驗：

1. 
   
   
2. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
      1. 
         支氣管擴張試驗：病人在吸入二劑短效支氣管擴張劑後15-20分鐘，其FEV₁增加12%以上且增加200ml以上，或是PEF增加15%以上，可診斷為氣喘。
         
      2. 
         尖峰呼氣流速（PEF）之早晚（間隔12小時）之變異度：若大於20%，表示氣喘控制不穩定。
         

1. 
   
   
2. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
      1. 
         
         
      2. 
         
         
      3. 
         運動試驗：用跑步機運動6分鐘後，若FEV1下降15%或PEF下降20%，可診斷運動誘發型氣喘。一般極限心率之90%為限。下列病人不宜行此試驗：a.心臟病或高血壓；b. FEV1<70%預估值；c.氣喘發作期；d.體弱和行動不便者。
         

兒童之預估公式為：

2.7 氣喘嚴重度之分類

2.8 吸入劑型之選擇

1. 
   
   
2. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
   6. 
      
      
   7. 
      
      
   8. 
      
      
      1. 
         五歲以下幼兒，應選擇定量噴霧器（MDI）連接輔助艙（spacer）和面罩，或者使用氣霧式噴霧器（nebulizer）。
         
      2. 
         五歲至七歲兒童，若不會直接使用定量噴霧器（MDI），可用乾粉吸入器（DPI），也可用氣霧式噴霧器。
         
      3. 
         七歲以上兒童，可用定量噴霧器（MDI），及乾粉吸入器（DPI），也可用氣霧式噴霧器。
         
      4. 
         嚴重發作時，應該使用定量噴霧器接輔助艙或者用氣霧式噴霧器。
         

圖一、氣喘的嚴重度分級及治療原則

2.9 治療

control 程度(表三) 做為參考，以作step up 或是 step down之決定。

表二

表三 2008 GINA(Global initiative for asthma)：Levels of asthma control

2.10 氣喘控制計劃

1. 
   
   
2. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
   6. 
      
      
   7. 
      
      
   8. 
      
      
   9. 
      
      
   10. 
       
       
       1. 
          教育病患以及家長
          針對氣喘的評估及治療教育病患並發展良好醫病關係
          
       2. 
          反覆評估以及監測
          每天記錄臨床症狀及肺功能測試以監測氣喘的嚴重度
          
       3. 
          避開氣喘誘發因素
          避開室內外過敏原及空氣污染源或是過敏食物及藥物
          
       4. 
          長期藥物治療計劃
          氣喘治療藥物分控制藥物及緩解藥物採階梯治療方式
          
       5. 
          急性發作處置計劃
          規劃及教育急性發作之居家處理方式尤其是藥物使用
          
       6. 
          提供長期追蹤照護
          指導正確用藥及環控評估成長運動飲食處置特殊情況
          

2.11 氣喘急性發作的處置計劃

如有下列情形，病人應立即送醫：

• 
  氣喘病嚴重到會死亡的高危險群病人。
  
• 
  急性發作很嚴重(如PEF小於最佳值的60%)。
  
• 
  使用支氣管擴張劑不能立即見效,或雖有藥效卻無法持續3小時。
  
• 
  使用皮質類固醇之後2-6小時仍未見改善。
  
• 
  病情進一步惡化。
  

圖二、氣喘急速惡化的治療 : 居家治療

評估嚴重度· 尖峰呼氣流速小於個人最佳值的80%· 臨床特徵 :咳嗽、呼吸困難、喘鳴、胸悶甚至使用呼吸輔助肌、出現胸骨上方凹陷 開始治療使用短效吸入式乙二型交感神經興奮劑每次2-4劑，更嚴重時每次4-10劑，此時可接輔助艙或以氣霧吸入，1小時內可用3次。
反應良好輕度發作尖峰呼氣流速大於預估值或最佳值之80%· 吸入乙二型交感神 經興奮劑有效達4小時以上· 可以繼續使用吸入式乙二型交感神經興奮劑每3-4小時一次，繼續24-48小時	反應不佳中度發作尖峰呼氣流速為預估值或最佳值之60-80%，症狀雖有改善，但藥效維持不到3小時· 加上口服類固醇每公斤體重0.5-1mg· 繼續使用吸入式乙二型交感神經興奮劑· 到門診求診	反應極差重度發作尖峰呼氣流速小於預估值或最佳值之60%，且症狀未見改善· 加上口服類固醇· 繼續使用吸入式乙二型交感神經興奮劑· 馬上到急診部求診
可與醫師討論回診的治療方式	當日儘快掛醫師的門診討論如何治療	直接到急診部
*病人若屬高危險群者，應該在開始自我處置後馬上與醫師連絡，因為有可能需要其他治療。

初期評估 ‧ 體檢(聽診、使用呼吸輔助肌、心跳次數、呼吸次數、PEF或FEV1、動脈血中氧氣濃度， 以及其他必要項目，如胸部X光看是否有肺炎、氣胸、縱膈氣腫、肺葉扁塌等)。   再度評估理學檢查、尖峰呼氣流速、血氣濃度及其他必須之檢驗 初期治療‧ 吸入式乙二型交感神經興奮劑，最好用氣霧(nebulizer)吸入，每二十分鐘吸入一劑，持續三劑。‧供氧至血氧飽和度大於90%(兒童大於95%)。‧病人若未立即改善，或近期內曾使用口服類固醇，或者此次發作嚴重，則應使用口服或注射之類固醇。‧急速惡化時，不可使用鎮靜劑。 中度發作‧尖峰呼氣流速為預估(最佳值)60-80%。‧體檢：中度症狀，使用呼吸輔助肌。‧每六十分鐘吸入交感神經興奮劑一劑。‧考慮使用類固醇。‧持續治療一至三小時。 重度發作‧尖峰呼氣流速為小於或等於預估(最佳值)60%。‧體檢：休息時有嚴重症狀，吸氣時胸部凹陷。‧病史：高危險群。‧初步治療後，未見改善。‧ 每小時(或持續)吸入式交感神經興奮劑，或再吸入抗乙醯膽鹼劑(Ipratropium)。‧氧氣。‧使用口服或注射類固醇。‧考慮皮下、肌肉或靜脈注射β2交感興奮劑。
反應良好‧前次治療後，療效持續60分鐘。‧體檢：正常，無不適。‧ 尖峰呼氣流速大於70%達一小時以上。‧血氧飽和度大於90％（小孩＞95％）	1～2小時內療效不良‧病史：高危險群‧體檢：輕微至中度症狀‧尖峰呼氣流速 50％-70％‧血氧飽和度未見改善。	1小時內反應欠佳‧病史：高危險群‧ 體檢：症狀嚴重、意識不清。‧尖峰呼氣流速小於30%。‧PCO2大於45mmHg。‧PO2小於60mmHg。
病人返家後 ‧ 繼續吸入乙二型交感神經興奮劑。 ‧多數情況可考慮使用短期之口服類固醇。 ‧教育病患： 1.正確用藥方法 2.複審治療計劃 3.密切追蹤	病人入院 ‧ 吸入乙二型交感神經興奮劑或加抗乙醯膽鹼劑(Ipratropium)。 ‧使用口服或注射類固醇。 ‧氧氣供應‧考慮注射aminophylline。 ‧ 監視尖峰呼氣流速，血氧濃度，脈搏及theophylline血中濃度。	送入加護病房 ‧ 吸入乙二型交感神經興奮劑或加抗抗乙醯膽鹼劑(Ipratropium)。 ‧注射類固醇。 ‧ 考慮皮下或靜脈注射β2興 奮劑。 ‧氧氣。 ‧考慮靜脈注射aminophylline ‧ 可能需要氣管插管或呼吸 器。
病情改善者 病情未改善者 返家照顧‧ 若尖峰呼氣流速大於70%持續1小時以上，病人應持續口服或吸入用藥。 住進加護病房‧六至十二小時內未見改善者，應加強照護。

2.12良好的氣喘治療要達到下列目標

• 
  持續控制氣喘症狀 ‧保持正常肺功能
  
• 
  保持正常的活動功能 ‧避免藥物副作用
  
• 
  避免不可逆的傷害 ‧避免死亡的發生
  
• 
  最輕微甚至沒有慢性症狀 ‧很少急性發作
  
• 
  不需要跑急診 ‧很少用到乙二型吸劑
  
• 
  活動沒有限制 ‧早晚尖峰流速差異小於20%
  
• 
  正常尖峰流速
  

3.1 General concepts

1. 
   
   
2. 
   
   
3. 
   
   
   1. 
      
      
      1. 
         Immunodeficiency should be suspected in any patient who has frequent or recurrent infections. However, immunodeficiency diseases are relatively uncommon and many other illnesses may predispose a patient to repeated infections.
         
      2. 
         In the 1920s some of the phenotypes of diseases which we now recognize as congenital immunodeficiencies were described. It was not until 1952 with Bruton’s description of congenital agammaglobulinemia that the first specific and characterized congenital immunodeficiency was described.
         
      3. 
         When there is no apparent explanation for the recurrent infections, a primary defect in host defense must be considered.
         
      4. 
         The primary immunodeficiencies generally are congenital and hereditary, so that most of the affected patients are infants or children.
         
      5. 
         Early diagnosis of primary immunodeficiencies is essential for prevention of irreversible end-organ damage from chronic infections.
         

3.2 分類

1. 
   
   
2. 
   
   
3. 
   
   
   1. 
      
      
   2. 
      
      
      1. 
         Primary immunodeficiency
         

• 
  Primary B-cell immunodeficiency:
  
• 
  Primary T-cell immunodeficiency:
  
• 
  Combined T and B-cell immunodeficiency
  
• 
  PMN dysfunction:
  
• 
  Complement deficiency:
  

2. 
   Secondary immunodeficiency: e.g. HIV infection, post-chemotherapy
   

3.3. The increased susceptibility to the microorganisms in the immunodeficiency

1. 
   
   
2. 
   
   
3. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
      1. 
         Humoral defects: encapsulated bacteria (sinopulmonary infections with pyogenic bacteria), enterovirus, and parasites
         
      2. 
         Cellular defects: opportunistic infections with viruses, Pneumocystis , and fungi
         
      3. 
         Phagocytic defects: pyogenic infections, particularly sinopulmonary and abscesses that involve the skin and LNs, and fungal infections
         
      4. 
         Complement defects: pyogenic infections, especially Neisseria infection, sepsis, or recurrent meningitis with encapsulated organisms.
         

3.4.1 Usually Present

• 
  Recurrent upper respiratory infections
  
• 
  Severe bacterial infections
  
• 
  Persistent infections with incomplete or no response to therapy
  

• 
  Failure to thrive or growth retardation
  
• 
  Infection with an unusual organism
  
• 
  Skin lesions (pyoderma, eczema,…)
  
• 
  Recalcitrant thrush
  
• 
  Diarrhea and malabsorption
  
• 
  Persistent sinusitis, mastoiditis
  
• 
  Recurrent bronchitis, pneumonia
  
• 
  Evidence of autoimmunity
  
• 
  Paucity of lymph nodes and tonsils
  
• 
  Hematologic abnormalities
  
• 
  Infection with unusual organism
  

• 
  Weight loss
  
• 
  Chronic conjunctivitis
  
• 
  Periodontitis
  
• 
  Lymphadenopathy
  
• 
  Hepatsplenomegaly
  
• 
  Severe viral disease
  
• 
  Chronic liver disease
  
• 
  UTI
  
• 
  Recurrent meningitis
  
• 
  Pyoderma gangrenosa
  
• 
  Cholangitis or hepatitis
  
• 
  Adverse reaction to vaccines
  
• 
  Bronchiectasis
  
• 
  Delayed umbilical cord detachment
  

3.5 Laboratory test for immunodeficiency

3.5.1 General

＊CBC + D/C: lymphocyte count (if nomal, T cell defect less likely),

neutrophil count, platelet count (smear for small platelet Wiskott-Aldrich

syndrome, Howell-Jolly bodiesasplenia)

＊ESR: elevation suggest chronic bacterial or fungal infection

＊Lateral skull X-ray for adenoid tissue: for X-linked agammaglobulinemia

＊IgG, IgA, IgM

＊IgG subclass: IgG1, IgG2, IgG3, IgG4

＊Antibodies to vaccines (eg: anti-Hib, anti-diphtheria IgG for IgG function)

＊Isohemagglutinin (eg. anti-A, anti-B for IgM function)

＊Lymphocyte subset:: Xlinked agammaglobulinemia (no circulating B cells)

＊Candida albicans intradermal skin test

＊Lymphocyte subset:, for B, T, NK cells subpopulation

＊Mitogen test:

＊Chest X-ray for thymic shadow: if no thymus in NB, consider DiGeorge

syndrome

＊Adhesion molecule (CD11b/CD18)

＊DHR test (dihydrorhodamine assay)

＊Phagotest

＊CH50

3.6.1 General policy

• 
  To maintain general health and nutrition
  
• 
  To prevent emotional problems related to their illness
  
• 
  To manage their numerous infectious episodes
  
• 
  Be protected from unnecessary exposure to infection
  
• 
  Killed vaccines should be given if there is evidence of some antibody synthesis
  
• 
  Long-term chronic antibiotic therapy may be of value
  
• 
  Have pulmonary function tests performed at regular intervals
  

3.6.2. Immunoglobulin supplement: for hypogammaglobulinemia (CVID,

Bruton’s disease): monthly IVIG 0.4g/kg/day, keep IgG level > 700 mg/dl

3.6.3.BMT: for T cell defect (Severe combined immunodeficiency, Wiskott-

Aldrich syndrome, DiGeorge syndrome, leukocyte adhesion defect), B

cell deficiency (X-linked lymphoproliferative disorder & CD40 ligand

defect), neutrophil defect (chronic granulomatous disease, Chediak-

Higashi syndrome)

• 
  Patients with suspected or proven T-cell immunodeficiencies should not be given routine blood transfusions because of the possibility of a G-V-H reaction from heterologous lymphocytes.
  
• 
  The blood should be irradiated prior to administration and it is advisable to use CMV-negative donors
  
• 
  Splenectomy is contraindicated
  
• 
  Corticosteroids should be used in these patients only with extreme caution.
  

• 
  Live attenuated vaccines should be avoided in all severe antibody or cellular immunodeficiencies because of the risk of vaccine-induced infection.
  
• 
  Paralytic poliomyelitis and prolonged poliovirus shedding from the gastrointestinal tract is a recognized complication of oral poliomyelitis vaccination in immunodeficiency.
  
• 
  Yearly influenza vaccination is also recommended for immunodeficient children who can make an antibody response and for family members of the immune-deficient child.
  
• 
  Parents, siblings, and other household members should not be given live poliomyelitis vaccine because of the increased risk of spread to the patient.
  
• 
  If live vaccines are given, systemic bacille Calmette-guerin infection, vaccinia gangrenosa, paralytic poliomyelitis, or giant cell (measles) pneumonia may develop in this patients.
  

(Hx& S/S: )

• 
  Morning stiffnessJRA, postinfectious arthritis
  
• 
  Facial rashes and joint complaints or weaknesslupus, dermatomyositis;
  
• 
  Raynaud phenomenon;scleroderma and overlapping syndromes
  
• 
  Trauma HxJRA, non-rheumatic disease, e.g. a torn meniscus, osteochondritis
  
• 
  Travel Hx, family enteric illness, sick petsreactive arthritis following enteric infection
  
• 
  Tick exposureLyme arthritis
  
• 
  Weaknessmuscular dystrophies, postviral illnesses, inflammatory myopathies ( JDM )
  
• 
  Gait problems osteopedic problems such as Perthes disease, JRA
  
• 
  Inability to walkmalignancy, osteomyelitis
  

(Normal joints should: look normal, and be bilaterally symmetric; assume a normal resting position; move smoothly an painlessly through the full range of motion.)

• 
  Lack of normal movementCNS, muscle, joint, skeletal problems
  
• 
  Decreased weightmalnutrition from inflammatory bowel disease
  
• 
  Tachycardiafever, carditis, pericarditis
  
• 
  Nailfold capillarosocopy; to detect vasculopathydermatomyositis, scleroderma…
  
• 
  Pericardial friction rubpericarditisSLE, systemic JRA;
  
• 
  Oral mucosal lesionsSLE, KD, Steven-J syndrome, scarlet fever
  
• 
  Eyes SLE (episcleritis), JRA (uveitis);
  
• 
  Arthritis with muscle weakness JDM, and MCTD;
  

4.3.1. ACR criteria: 11 項中至少有 4 項符合,就要開始治療,不足4項者也要考慮治療

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
      1. 
         
         
         1. 
            malar rash
            
         2. 
            discoid-lupus rash
            
         3. 
            photosensitivity
            
         4. 
            oral or nasal mucocutaneous ulcers
            
         5. 
            non-erosive arthritis
            
         6. 
            serositis: pleural effusion, pericardial effusion
            
         7. 
            Nephritis: proteinuria >0.5g/d, cellular casets
            
         8. 
            Neurologic disorder: encephalopathy ( seizure, psychosis )
            
         9. 
            Hematologic disorder ( lymphopenia, anemia, thrombocytopenia)
            
         10. 
             positive immyunoserology :
             

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
      1. 
         
         
         1. 
            
            
         2. 
            
            
         3. 
            
            
         4. 
            
            
         5. 
            
            
         6. 
            
            
         7. 
            
            
         8. 
            
            
         9. 
            
            
         10. 
             
             
             1. 
                anti-dsDNA antibody
                
             2. 
                anti-Sm antibody
                
             3. 
                positive finding of antiphospholipid antibodies based on :
                

• 
  false VDRL for at least 6 months, confirmed by TPHA, or
  
• 
  positive antiphospholipid antibody, or
  
• 
  anticardiolipin antibodies IgG or IgM, or
  
• 
  Lupus anticoagulant
  

11. 
    positive ANA
    

4.3.2 Lab:

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
      1. 
         
         
      2. 
         
         
         1. 
            Old cases: CBC D/C, 生化, CRP, ESR, C3, C4, anti-dsDNA, U/A
            
         2. 
            Fresh cases: ANA, anti-ENA, antiphospholipid Ab (APA), anticardiolipin Ab(ACA), VDRL 等等
            

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
      1. 
         
         
      2. 
         
         
      3. 
         
         
         1. 
            plaquenil: for mild manifestations, except G6PD Hx
            
         2. 
            NSAID: for arthralgia and arthritis
            
         3. 
            Steroid: to control autoimmune dysregulation activities
            
         4. 
            Others: azathioprine, cyclophosphamide(Endoxan), 等..
            
         5. 
            Steroid pulse therapy: acute relief of severe illness(CNS, hematologic crisis, acute lupus pneumonitis, lupus nephritis)
            
         6. 
            Endoxan pulse therapy: maintenance therapy for severe illness( CNS, hematological crisis, acute lupus pneumonitis, lupus nephritis (Class 4))
            

4.4 HSP, Henoch-Schonlein Purpura

4.4.1. American College of Rheumatology 1990 criteria: at least 2 criteria met

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
      1. 
         
         
         1. 
            palpable purpura
            
         2. 
            age <20 years old at disease onset
            
         3. 
            bowel angina: abdominal pain or positive stool occult blood
            
         4. 
            granulocyte infiltration of skin biopsy
            

Fresh 病人給藥前 work-up:

• 
  CBC/DC, ANA, C3, C4, IgA, IgG, IgM, ASLO, ESR
  
• 
  nasopharyngeal swab for virus isolation, throat swab for GAS
  
• 
  U/A, stool OB
  

4.4.3 Treatment

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
      1. 
         
         
      2. 
         
         
      3. 
         
         
         1. 
            consider NSAID
            
         2. 
            consider Prednisolone for renal , CNS involvement or severe GI tract or other organ involvement
            

4.5 Juvenile dermatomyositis (JDM)

4.5.1 Diagnostic criteria

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
      1. 
         
         
         1. 
            Symmetric weakness of the proximal muscle
            
         2. 
            Characteristic cutaneous changes consisting: Heliotrope sign, Gottron sign
            
         3. 
            Elevation of muscle enzyme
            
         4. 
            EMG: myopathy and denervation
            
         5. 
            Muscle biopsy: necrosis and inflammation
            

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
      1. 
         
         
      2. 
         
         
         1. 
            Old cases: CBC + D/C, 生化, CRP, ESR, vWF Ag, Muscle enzymes(GOT, LDH, CPK)
            
         2. 
            Fresh cases: may check ANA, anti-dsDNA(EIA), anti-ENA
            

4.5.3. Treatment:

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
      1. 
         
         
      2. 
         
         
      3. 
         
         
         1. 
            Sunscreen
            
         2. 
            Vit D: to repair osteopenia
            
         3. 
            Hydroxychloroquine
            
         4. 
            steroid:
            For mild case, hydroxychloroquine with low-dose steroid 0.5-1mg/kg/day);
            For general case, oral steroid 1-2mg/kg/day;
            For severe case, may give immunosuppressant, or pulse steroid therapy.
            
         5. 
            Immunosuppressant: azathioprine, cyclosporin, methotrexate, cyclophosphamide.
            
         6. 
            IVIG: 1g/kg/day for 2 days, monthly, for 2 years。
            

4.6 JRA, Juvenile Rheumatoid Arthritis

4.6.1 Diagnostic criteria:

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
   6. 
      
      
      1. 
         
         
         1. 
            Age at onset< 16 y/o
            
         2. 
            Arthritis in one or more joints
            
         3. 
            duration of disease: 6 weeks or longer
            
         4. 
            three types (defined by type of disease in the first 6 mo )
            

• 
  Polyarthritis: 5 or more inflamed joints
  
• 
  Oligoarthritis: <5 inflamed joints
  
• 
  Systemic: arthritis with characteristic fever
  

5. 
   Exclusion of other diseases
   

• 
  Old cases: CBC + D/C, 生化, CRP, ESR, C3, C4, ANA,
  
• 
  Fresh case: Rheumatoid factor( RF) , HLA-B27
  

• 
  NSAID
  
• 
  DMARD: salfasalazine, methotrexate, azathioprine ( Imuran), cyclophosphamide ( Endoxan )
  
• 
  Steroid: for overwhelming inflammatory or systemic illness, or as bridge therapy
  

4.7 Rheumatology medications

Dosage form: 250mg tablet

Dosage: 10-15 mg/kg/day given in 2 divided doses
4.7.2 Prednisolone

Dosage form: 5 mg tablet; Kidsolone solution (1mg/mL) (<5y/o)

Dosage:

Anti-inflammatory or Immunosuppressive effects: 1-2mg/kg/day

Acute asthma: 1-2mg/kg/day divided 1 to 2 times daily for 3 to 5 days.

Methylprednisolone

Dosage form: IV form 40 mg/vial

Dosage:

Anti-inflammatory or immunosuppressive: 0.5-1.7mg/kg/day divided

Status asthmaticus: 2mg/kg/dose (loading); additional 0.5-

1mg/kg/dose every 6 hours (maintain).

Methylprednisolone 4 mg is equivalent to Prednisolone 5 mg )

Dosage form: 200 mg tablet

Dosage: JRA or SLE: 3-5 mg/kg/day divided 1-2 time/day; maximum 400

mg/day

pigmentation,

agranulocytosis
4.7.4 Sulfasalazine

Dosage form: 500 mg enteric-coated tablet

Dosage: 30-50 mg /kg/day twice daily; maximum 2 grams/day

Adverse Effects: headache, N/V, rash, hepatotoxicity, nephrotoxicity

Dosage form: 50 mg tablet

Dosage: initial 1 mg/kg/day po once daily or divided twice, increase

by 0.5 mg/kg/day every 4 weeks, maximum 2-3 mg/kg/day.

Adverse Effects: gastrointestinal upset, N/V, BM suppression.
4.7.6 Cyclosporine

Dosage form: solution (Sandimmune Neoral) 100 mg/ml; capsule

(Sandimmune Neoral) 25 mg/cap or 100 mg/cap

Dosage: 3 to 5 mg/kg/day (adjust according to serum trough level 100

ng/mL)

Adverse Effects: nephrotoxicity, tremor, hirsutism, and hypertension.

Dosage form: 250 mg/cap

Dosage: initial 600 mg/BSA (M2)/dose twice daily; maximum 2 gm/day.

Adverse Effects: myelosuppression, constipation, diarrhea, N/V,

headache, hypertension (28%-32%)
4.7.8 Methylprednisolone Pulse Therapy

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
   6. 
      
      
   7. 
      
      
      1. 
         
         
      2. 
         
         
      3. 
         
         
      4. 
         
         
      5. 
         
         
      6. 
         
         
      7. 
         
         
      8. 
         
         
         1. 
            Adequate dose of Methylprednisolone (30mg/kg, maximum 1g) in 100ml D5W iv drip for 2-3 hours qd .
            
         2. 
            Check BP before each methylprednisolone, then q1h x 3,
            
         3. 
            Record I/O,
            
         4. 
            Check urine sugar qd.
            
         5. 
            BW < 10 kg, I/O > +500 ml; BW > 10 kg, I/O > +1000 ml, inform doctor
            

＊Cardiac arrhythmia secondary to potassium depletion

＊Hypertension secondary to sodium retention

＊Acute psychosis, convulsions

＊Hyperglycemia with or without ketosis

＊Gastrointestinal hemorrhage

＊Anaphylaxis

＊Infection

＊Osteonecrosis
4.7.9 Cyclophosphamide (Endoxan) Pulse Therapy

1. 
   
   
2. 
   
   
3. 
   
   
4. 
   
   
   1. 
      
      
   2. 
      
      
   3. 
      
      
   4. 
      
      
   5. 
      
      
   6. 
      
      
   7. 
      
      
      1. 
         
         
      2. 
         
         
      3. 
         
         
      4. 
         
         
      5. 
         
         
      6. 
         
         
      7. 
         
         
      8. 
         
         
      9. 
         
         
         1. 
            Hydration with 2.5% G/S + sodium bicarbonate 1amp keep ml/hr from 3hr before to 24 hr after therapy
            
         2. 
            Record I/O qd,
            
         3. 
            Collect 12hr urine protein and 12hr CCr since
            
         4. 
            Check CBC+D/C, BUN, Cre, TG, CHO, Alb, GOT, GPT, C3, C4, antidsDNA
            
         5. 
            Adequate dose of Cyclophosphamide (500-1000mg/m2) mg in D5W 150ml iv drip > 1 hr.
            
         6. 
            Mesna mg (200-400mg/m2) iv push start 30 min before cyclophosphamide then q6h X 3 doses.
            
         7. 
            Check U/A qd.
            
         8. 
            Primperan (0.1-0.2mg/kg, Max 10mg) mg iv push start 30 min before chemotherapy then q8h.
            

＊Hydration rate 為maintain fluid 1.5 倍, max rate 100ml/hr, 並視病人之oral

intake 而調整, 若urine output > 3000ml/m2-day (max. 4000ml/day), 即可降

低 hydration rate

＊BW < 10kg, I/O > +500ml; BW > 10 kg, I/O > +1000ml, inform doctor. May

give Lasix, if there is no response, decrease hydration amount (注意pulmonary edema)

＊For those with inadequate urine output during therapy or severe edema

before therapy, continuous bladder irrigation with a three-way foley

catheter (N/S run 100ml/hr with clamp)

＊Cyclophosphamide starting dose:

if CCr > 1/3 of normal value, start with 500mg/m2

if CCr < 1/3 of normal value, start with 300mg/m2

＊Cyclophosphamide escalation dose:

if nadir WBC > 4000/mm3, ↑ subsequent dose by 250mg/m2 (max: 1000

mg/m2), if nadir WBC < 4000/mm3, ↓ subsequent dose by 250mg/m2

＊Mesna dose: 40% of cyclophosphamide dose for 4 doses

＊Cyclophosphamide 會引起 hemorrhagic cystitis，必須以Mesna +

Hydration + Alkalization 來預防，如果仍不幸發生hemorrhagic cystitis，則

必須增加hydration rate 及把Mesna 加倍，並延長時間到hemorrhagic

cystitis 消失後一天；若病人之前就有hemorrhagic cystitis history，則一開

始即必須增加hydration rate 及Mesna dosage。

＊Check nadir white count at 10-14 days after Endoxan pulse therapy

＊Protocol: monthly dose for 6 months, followed by every-3-month course

for 18 months

＊On admission, if WBC still < 4000 or ANC < 2500 hold therapy