大四下學(xué)期11級(jí)兒科川崎病

1、 川崎病(Kawasaki Disease) The Pediatric Department The First Teaching Hospital of Z.Z.U.Jindou An一、概述（General Considerations） Kawasaki Disease（KD，川崎病）is also called mucocutaneous lymph node syndrome（皮膚粘膜淋巴結(jié)綜合征） first described by Dr. Tomisaku Kawasaki in Japan in 1967.是一種病因未明的以全身血管炎變?yōu)橹饕±淼募毙园l(fā)熱性出疹性疾??；It

2、 is an acute disease with fever and rash, which main pathological change is the middle and small arteritis in human body. 對(duì)兒童最嚴(yán)重的損害是冠狀動(dòng)脈受損導(dǎo)致的冠狀動(dòng)脈擴(kuò)張和冠狀動(dòng)脈瘤。 The most severe damage to the children is the dilatation of the coronary artery and the coronary aneurysms), which is caused by injury of the cor

3、onary artery.嚴(yán)重病例潛在的風(fēng)險(xiǎn)是冠狀動(dòng)脈血栓或狹窄、心肌梗塞、動(dòng)脈瘤破裂、猝死。 The potential risks for severely affected patients are the coronary artery thrombosis or stenosis, myocardial infarction, neurysm rupture, and sudden death.發(fā)病年齡： 大于3個(gè)月的嬰兒及幼兒易患該病 80%的病例年齡在5歲以下 成人罕見(jiàn)Age of onset: The 3 months-infants and toddlers are easy

4、 to suffer from the disease, 80% of the cases occurred in children under 5 years old. It is very rare in adults.發(fā)病性別： 男孩多于女孩，男:女= 1.5:1Sex of onset: It is more common in boys than in girls, which ratio is 1.5:1.發(fā)病地區(qū)： 世界各地均有發(fā)病，但亞洲發(fā)病率最高Region of onset: The disorder occurs worldwide, with Asians at hig

5、hest risk.二、病因與發(fā)病機(jī)制（Etiology and Pathogenesis ）病因不清，但根據(jù)其流行病學(xué)及臨床特征，高度提示其為感染因素。The cause of the illness remains unknown, but epidemiologic and clinical features strongly support an infectious origin. 這些特征包括小年齡兒童患病、呈波浪型的地區(qū)流行、具有自限性。These features include the young age group affected, epidemics with wave

6、like geographic spread of illness, the self-limited nature. Nonetheless, it is unusual to have multiple cases present at the same time from a family or day care center. One hypothesis is that a ubiquitous(普遍存在的) childhood infectious agent causes Kawasaki disease.在部分病例，其父母年幼時(shí)曾患過(guò)川崎病。Kawasaki disease h

7、as recurred in families when previously affected parents have children who develop the disease. 具有CCRS基因突變的兒童易患川崎病， CCRS編碼對(duì)炎癥趨化因子CCL.3， CCL3L1有高親和力的受體。Genetic variation of CCRS,which encodes a high-affinity receptor for the chemokines CCL.3 and CCL3L1, suggests an influential role of gene-gene inter

8、actions for susceptibility to Kawasaki disease.The pathogenesis of the illness also remains unknown. 可能的機(jī)制是： 中毒性休克綜合征毒素(toxic shock syndrome toxin, TSST)和表皮剝脫性毒素(exfoliative toxin, ET)、鏈球菌致熱外毒素(streptococcal pyrogenic exotoxins, SPE)等，細(xì)菌熱休克蛋白(heat shock protein, HSP)65T細(xì)胞異?；罨?abnormal activation)及細(xì)胞

9、因子(cytokine)的級(jí)聯(lián)放大 效應(yīng)(cascade amplification effect) 血管內(nèi)皮損傷(vascular endothelium injury)、平滑肌細(xì)胞及膠原組織增生(collagen tissue hyperplasia)等冠狀動(dòng)脈病變。 冠狀動(dòng)脈擴(kuò)張(dilatation of the coronary artery) 冠狀動(dòng)脈瘤(coronary aneurysms) 冠狀動(dòng)脈狹窄及血栓(coronary artery stenosis or thrombosis)三、病理（Pathology）冠狀動(dòng)脈擴(kuò)張(dilatation of the corona

10、ry artery)及冠狀動(dòng)脈瘤(coronary aneurysms)的發(fā)生率： 在10天內(nèi)未經(jīng)及時(shí)治療者為25%40% 經(jīng)大劑量丙種球蛋白(immunoglobulin/ gamma globulin)治療者為15%。川崎病的基本病理變化為全身性血管炎(general vasculitis)累及主動(dòng)脈及其分支，好發(fā)于冠狀動(dòng)脈，其病理改變可分為四期：第期 約19天，小動(dòng)脈周?chē)l(fā)生急性炎癥反應(yīng)，有中性粒細(xì)胞(neutrophil)、嗜酸性粒細(xì)胞(eosinophil)及淋巴細(xì)胞(lymphocyte)浸潤(rùn)(infiltrate) ；第期 1021天，冠狀動(dòng)脈主要分支等中等大小動(dòng)脈全層血管炎，有

11、炎性細(xì)胞浸潤(rùn)（inflammatory cell infiltrate），伴壞死（necrosis）及水腫（edema），彈力纖維（elastic fibers）和肌層（muscular layer）斷裂(rupture)，可形成血栓（thrombosis）及動(dòng)脈瘤（aneurysms）；第期 2831天，炎癥逐漸消退，血栓（thrombosis）及肉芽（granulation）形成，纖維組織增生（fibroplasia），內(nèi)膜（endomembrane）明顯增厚，導(dǎo)致冠狀動(dòng)脈部分或完全阻塞（blockage）；第期 長(zhǎng)達(dá)數(shù)年，病變逐漸愈合，心肌瘢痕（myocardial scar）形成，阻塞

12、可能再通（recanalization）。四、臨床表現(xiàn)（Clinical Manifestations） 1.主要表現(xiàn)(Main Manifestations) (1)發(fā)熱（ Fever ） 發(fā)熱持續(xù)5天以上，常為弛張熱，對(duì)抗生素治療無(wú)效。 Fever persists over 5 days, and is characteristically high (39C or higher), remittent and unresponsive to antibiotics. 未經(jīng)治療的病例，發(fā)熱一般持續(xù)1-2周，有時(shí)可長(zhǎng)達(dá)3-4周。持續(xù)的發(fā)熱，往往提示有可能發(fā)生冠狀動(dòng)脈病變。The durat

13、ion of fever without treatment is generally 1-2 wk, but it may persist for 3-4 wk. Prolonged fever is prognostic for the development of coronary artery disease. (2)眼球結(jié)膜充血 bilateral bulbar conjunctival injection, usually without exudate（滲出物）. (3)口唇充血皸裂，口咽粘膜彌漫充血，草莓舌 cracked lips, erythema of the oral

14、and pharyngeal mucosa with strawberry tongue and dry. (4)手足硬性水腫、紅斑，edema and erythema of the hands and feet; 指、趾甲與皮膚交界處膜狀脫皮 Periungual desquamation of the fingers and toes begins 1-3 wk after the onset of illness and may progress to involve the entire hand and foot. (5)多形性皮疹 rash of various forms (斑

15、丘疹 maculopapular, 多形性紅斑 erythema multiforme, or 猩紅熱樣皮疹 scarlatiniform) with accentuation in the groin area（腹股溝）; It appears 2-4 days after onset of the fever, and persists 4-5 days. 肛周皮膚發(fā)紅、脫皮 erythema，desquamation in perianal area.1 (6)非化膿性頸淋巴結(jié)腫大 nonsuppurative cervical lymphadenopathy 通常為單側(cè) usually

16、 uni-lateral 直徑1.5 cm with node size of 1.5 cm2.次要表現(xiàn)（Secondary Manifestations） Include 患兒易激惹，尤其是嬰兒 extreme irritability that is especially prominent in infants 無(wú)菌性腦膜炎 aseptic meningitis 腹瀉 diarrhea 輕度的肝炎 mild hepatitis 膽囊的水腫 hydrops of the gallbladder 尿道炎 urethritis 尿道口炎 meatitis 無(wú)菌性膿尿 sterile pyuri

17、a 中耳炎 otitis media, and 關(guān)節(jié)炎 arthritis. Cardiac involvement is the most important manifestation of Kawasaki disease, which includes: 心肌炎 myocarditis, manifested as tachycardia, decreased ventricular function心包炎 pericarditis冠狀動(dòng)脈擴(kuò)張 dilitation of the coronary artery冠狀動(dòng)脈瘤 coronary artery aneurysms Giant

18、coronary artery aneurysms (28 mm internal diameter) pose the greatest risk for破裂 rupture, 血栓 thrombosis or 狹窄 stenosis, and 心肌梗塞 myocardial infarction.五、輔助檢查(Laboratory Findings)血液學(xué)檢查(Hematologic Test) The leukocyte count is normal to elevated with a predominance of neutrophils and 核左移 immature form

19、s. 正常細(xì)胞Normocytic and 正色素 normochromic anemia is common. Elevated ESR, CRP are almost universally present in the acute phase of the illness and may persist 4-6 wk. ALT, AST may increase. The platelet count is generally normal in the 1st week of illness and rapidly increases by the 2nd-3rd wk of illn

20、ess, sometimes exceeding l,000,000/mm3.2.免疫學(xué)檢查(immunologic test) The IgG, IgM,IgA in the serum is elevated.3.ECGsinus tachycardia (竇性心動(dòng)過(guò)速) nonspecific changes of the ST-TElevated ST and low voltage of QRS occurs in the cases with pericarditis(心包炎). The remarkable elevated ST, upside down T waves and

21、 abnormal Q could be found in the kids with myocardial infarction (心肌梗死).4.胸部X線片(chest x-ray film) The lamellar shadow(片狀陰影) and large heart could be found occasionally.5.超聲心動(dòng)圖(echocardiogram) A small pericardial effusion（心包積液） is common during the acute illnes. Significant valvular regurgitation （瓣

22、膜反流）The systemic artery aneurysms may occur, but are mon. If the coronary artery was injured, the dilitation of the coronary artery(冠狀動(dòng)脈擴(kuò)張), coronary artery aneurysms(冠狀動(dòng)脈瘤) and coronary artery stenosis(冠狀動(dòng)脈狹窄) could happen.冠狀動(dòng)脈擴(kuò)張的標(biāo)準(zhǔn)較多采用的是按年齡分段的冠狀動(dòng)脈擴(kuò)張標(biāo)準(zhǔn)：歲冠脈直徑2.mm；歲冠脈直徑3.mm；歲冠脈直徑3.5 mm。冠狀動(dòng)脈局部擴(kuò)張階段與相鄰內(nèi)

23、經(jīng)比值超過(guò)1.為冠狀動(dòng)脈瘤；6.冠狀動(dòng)脈造影術(shù) The coronary angiography should be performed, when the multiple artery aneurysms were found by echocardiogram, or the ECG revealed the myocardial ischemia（心肌缺血）. 六、診斷標(biāo)準(zhǔn)(diagnostic criteria) 不明原因發(fā)熱5天以上，伴下列5項(xiàng)中4項(xiàng)者，排除其它疾病后，可確診為完全性川崎?。?1)周?chē)w的變化：急性期掌跖紅斑，手足硬性水腫；恢復(fù)期指趾端膜狀脫皮(2)多形性紅斑(3

24、)非化膿性眼結(jié)合膜充血(4)口唇充血皸裂，口腔粘膜彌漫充血，草莓舌(5)非化膿性頸淋巴結(jié)腫大（直徑大約1.5cm）不典型或不完全性川崎病患兒，除有持續(xù)發(fā)熱外，只有上述5項(xiàng)中的3項(xiàng)及3項(xiàng)以下，但超聲心動(dòng)圖顯示為冠狀動(dòng)脈擴(kuò)張或冠狀動(dòng)脈瘤。In atypical or plete Kawasaki disease, the patient has persistent fever but with fewer than four other features of the illness and with the dilitation of the coronary artery, coronary

25、 artery aneurysms found by echocardiagram. 對(duì)臨床醫(yī)生來(lái)說(shuō)，確診不完全性川崎病是一個(gè)挑戰(zhàn)。不完全性川崎病常發(fā)生在嬰兒，且易發(fā)生冠狀動(dòng)脈病變。Accurate identification of plete cases is a major clinical challenge. plete cases are most frequent in infants, who, unfortunately, also have the highest likelihood of developing coronary artery disease.七、鑒別診斷

26、(differential diagnosis)1細(xì)菌性敗血癥(bacterial septicemia ) 血培養(yǎng)陽(yáng)性，抗生素治療有效，可發(fā)現(xiàn)原發(fā)感染灶；2幼年型類(lèi)風(fēng)濕關(guān)節(jié)炎（全身型）(juvenile rheumatoid arthritis) 有持續(xù)高熱、皮疹、肝脾淋巴結(jié)腫大及關(guān)節(jié)痛，無(wú)結(jié)膜充血、口唇鄆裂、手足硬性水腫及指趾端膜狀脫皮，無(wú)冠狀動(dòng)脈擴(kuò)張；3猩紅熱(scarlet fever) 多于發(fā)熱當(dāng)日或次日出疹，為粟粒樣丘疹，疹間皮膚潮紅，可見(jiàn)貧血性皮膚劃痕、帕氏線、楊梅樣舌、口周蒼白圈，無(wú)結(jié)膜充血、手足硬性水腫及指趾端膜狀脫皮，口唇鄆裂不明顯，無(wú)冠狀動(dòng)脈擴(kuò)張，青霉素治療有效；4滲出性

27、多形紅斑(erythema multiforme exudativu, Stevens-Johnson syndrome) 皮疹范圍廣，多為皰疹，皮膚糜爛出血，有口腔潰瘍。八、治療（treatment）1控制炎癥(control of inflammation)（1）阿司匹林(aspirin) 30100mg/(kgd),分34次口服 熱退后3天開(kāi)始逐漸減量，熱退2周左右減至35mg/(kgd),維持68周； 如有冠狀動(dòng)脈病變，應(yīng)持續(xù)用藥至冠狀動(dòng)脈恢復(fù)正常。（2）靜脈用丙種球蛋白(intravenous immunoglobulin,IVIG) 應(yīng)在發(fā)病早期(10天內(nèi))用IVIG 2g/kg于812h左右緩慢靜脈滴注 如果IVIG治療后仍發(fā)熱（體溫 38），持續(xù)4872h及CRP等未改善者,為IVIG治療無(wú)反應(yīng)，可再用IVIG12g/kg，一次靜脈滴注，同時(shí)應(yīng)用腎上腺皮質(zhì)激素治療。（3）腎上腺皮質(zhì)激素(adrenal cortex hormone)適應(yīng)證(indications) A.合并全心炎；B.無(wú)法得到大劑量IVIG；C.對(duì)大劑量IVIG不反應(yīng)且病情難以控制者。應(yīng)用方法(application methods) 可考慮與阿司匹林(aspirin)和雙嘧達(dá)莫（dipyridamole,潘生丁persantine）聯(lián)合應(yīng)用常用潑尼松(prednisone)12mg/