大四下学期11级儿科川崎病

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（皮肤粘膜淋巴结综合征） first described by Dr. Tomisaku Kawasaki in Japan in 1967.是一种病因未明的以全身血管炎变为主要病理的急性发热性出疹性疾病；It

2、 is an acute disease with fever and rash, which main pathological change is the middle and small arteritis in human body. 对儿童最严重的损害是冠状动脉受损导致的冠状动脉扩张和冠状动脉瘤。 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.严重病例潜在的风险是冠状动脉血栓或狭窄、心肌梗塞、动脉瘤破裂、猝死。 The potential risks for severely affected patients are the coronary artery thrombosis or stenosis, myocardial infarction, neurysm rupture, and sudden death.发病年龄： 大于3个月的婴儿及幼儿易患该病 80%的病例年龄在5岁以下 成人罕见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.发病性别： 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.发病地区： 世界各地均有发病，但亚洲发病率最高Region of onset: The disorder occurs worldwide, with Asians at hig

5、hest risk.二、病因与发病机制（Etiology and Pathogenesis ）病因不清，但根据其流行病学及临床特征，高度提示其为感染因素。The cause of the illness remains unknown, but epidemiologic and clinical features strongly support an infectious origin. 这些特征包括小年龄儿童患病、呈波浪型的地区流行、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，其父母年幼时曾患过川崎病。Kawasaki disease h

7、as recurred in families when previously affected parents have children who develop the disease. 具有CCRS基因突变的儿童易患川崎病， CCRS编码对炎症趋化因子CCL.3， CCL3L1有高亲和力的受体。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. 可能的机制是： 中毒性休克综合征毒素(toxic shock syndrome toxin, TSST)和表皮剥脱性毒素(exfoliative toxin, ET)、链球菌致热外毒素(streptococcal pyrogenic exotoxins, SPE)等，细菌热休克蛋白(heat shock protein, HSP)65T细胞异常活化(abnormal activation)及细胞

9、因子(cytokine)的级联放大 效应(cascade amplification effect) 血管内皮损伤(vascular endothelium injury)、平滑肌细胞及胶原组织增生(collagen tissue hyperplasia)等冠状动脉病变。 冠状动脉扩张(dilatation of the coronary artery) 冠状动脉瘤(coronary aneurysms) 冠状动脉狭窄及血栓(coronary artery stenosis or thrombosis)三、病理（Pathology）冠状动脉扩张(dilatation of the corona

10、ry artery)及冠状动脉瘤(coronary aneurysms)的发生率： 在10天内未经及时治疗者为25%40% 经大剂量丙种球蛋白(immunoglobulin/ gamma globulin)治疗者为15%。川崎病的基本病理变化为全身性血管炎(general vasculitis)累及主动脉及其分支，好发于冠状动脉，其病理改变可分为四期：第期 约19天，小动脉周围发生急性炎症反应，有中性粒细胞(neutrophil)、嗜酸性粒细胞(eosinophil)及淋巴细胞(lymphocyte)浸润(infiltrate) ；第期 1021天，冠状动脉主要分支等中等大小动脉全层血管炎，有

11、炎性细胞浸润（inflammatory cell infiltrate），伴坏死（necrosis）及水肿（edema），弹力纤维（elastic fibers）和肌层（muscular layer）断裂(rupture)，可形成血栓（thrombosis）及动脉瘤（aneurysms）；第期 2831天，炎症逐渐消退，血栓（thrombosis）及肉芽（granulation）形成，纤维组织增生（fibroplasia），内膜（endomembrane）明显增厚，导致冠状动脉部分或完全阻塞（blockage）；第期 长达数年，病变逐渐愈合，心肌瘢痕（myocardial scar）形成，阻塞

12、可能再通（recanalization）。四、临床表现（Clinical Manifestations） 1.主要表现(Main Manifestations) (1)发热（ Fever ） 发热持续5天以上，常为弛张热，对抗生素治疗无效。 Fever persists over 5 days, and is characteristically high (39C or higher), remittent and unresponsive to antibiotics. 未经治疗的病例，发热一般持续1-2周，有时可长达3-4周。持续的发热，往往提示有可能发生冠状动脉病变。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)眼球结膜充血 bilateral bulbar conjunctival injection, usually without exudate（渗出物）. (3)口唇充血皲裂，口咽粘膜弥漫充血，草莓舌 cracked lips, erythema of the oral

14、and pharyngeal mucosa with strawberry tongue and dry. (4)手足硬性水肿、红斑，edema and erythema of the hands and feet; 指、趾甲与皮肤交界处膜状脱皮 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, 多形性红斑 erythema multiforme, or 猩红热样皮疹 scarlatiniform) with accentuation in the groin area（腹股沟）; It appears 2-4 days after onset of the fever, and persists 4-5 days. 肛周皮肤发红、脱皮 erythema，desquamation in perianal area.1 (6)非化脓性颈淋巴结肿大 nonsuppurative cervical lymphadenopathy 通常为单侧 usually

16、 uni-lateral 直径1.5 cm with node size of 1.5 cm2.次要表现（Secondary Manifestations） Include 患儿易激惹，尤其是婴儿 extreme irritability that is especially prominent in infants 无菌性脑膜炎 aseptic meningitis 腹泻 diarrhea 轻度的肝炎 mild hepatitis 胆囊的水肿 hydrops of the gallbladder 尿道炎 urethritis 尿道口炎 meatitis 无菌性脓尿 sterile pyuri

17、a 中耳炎 otitis media, and 关节炎 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冠状动脉扩张 dilitation of the coronary artery冠状动脉瘤 coronary artery aneurysms Giant

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

19、s. 正常细胞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.免疫学检查(immunologic test) The IgG, IgM,IgA in the serum is elevated.3.ECGsinus tachycardia (窦性心动过速) 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线片(chest x-ray film) The lamellar shadow(片状阴影) and large heart could be found occasionally.5.超声心动图(echocardiogram) A small pericardial effusion（心包积液） 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(冠状动脉扩张), coronary artery aneurysms(冠状动脉瘤) and coronary artery stenosis(冠状动脉狭窄) could happen.冠状动脉扩张的标准较多采用的是按年龄分段的冠状动脉扩张标准：岁冠脉直径2.mm；岁冠脉直径3.mm；岁冠脉直径3.5 mm。冠状动脉局部扩张阶段与相邻内

23、经比值超过1.为冠状动脉瘤；6.冠状动脉造影术 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、诊断标准(diagnostic criteria) 不明原因发热5天以上，伴下列5项中4项者，排除其它疾病后，可确诊为完全性川崎病：(1)周围肢体的变化：急性期掌跖红斑，手足硬性水肿；恢复期指趾端膜状脱皮(2)多形性红斑(3

24、)非化脓性眼结合膜充血(4)口唇充血皲裂，口腔粘膜弥漫充血，草莓舌(5)非化脓性颈淋巴结肿大（直径大约1.5cm）不典型或不完全性川崎病患儿，除有持续发热外，只有上述5项中的3项及3项以下，但超声心动图显示为冠状动脉扩张或冠状动脉瘤。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. 对临床医生来说，确诊不完全性川崎病是一个挑战。不完全性川崎病常发生在婴儿，且易发生冠状动脉病变。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、鉴别诊断

26、(differential diagnosis)1细菌性败血症(bacterial septicemia ) 血培养阳性，抗生素治疗有效，可发现原发感染灶；2幼年型类风湿关节炎（全身型）(juvenile rheumatoid arthritis) 有持续高热、皮疹、肝脾淋巴结肿大及关节痛，无结膜充血、口唇郓裂、手足硬性水肿及指趾端膜状脱皮，无冠状动脉扩张；3猩红热(scarlet fever) 多于发热当日或次日出疹，为粟粒样丘疹，疹间皮肤潮红，可见贫血性皮肤划痕、帕氏线、杨梅样舌、口周苍白圈，无结膜充血、手足硬性水肿及指趾端膜状脱皮，口唇郓裂不明显，无冠状动脉扩张，青霉素治疗有效；4渗出性

27、多形红斑(erythema multiforme exudativu, Stevens-Johnson syndrome) 皮疹范围广，多为疱疹，皮肤糜烂出血，有口腔溃疡。八、治疗（treatment）1控制炎症(control of inflammation)（1）阿司匹林(aspirin) 30100mg/(kgd),分34次口服 热退后3天开始逐渐减量，热退2周左右减至35mg/(kgd),维持68周； 如有冠状动脉病变，应持续用药至冠状动脉恢复正常。（2）静脉用丙种球蛋白(intravenous immunoglobulin,IVIG) 应在发病早期(10天内)用IVIG 2g/kg于812h左右缓慢静脉滴注 如果IVIG治疗后仍发热（体温 38），持续4872h及CRP等未改善者,为IVIG治疗无反应，可再用IVIG12g/kg，一次静脉滴注，同时应用肾上腺皮质激素治疗。（3）肾上腺皮质激素(adrenal cortex hormone)适应证(indications) A.合并全心炎；B.无法得到大剂量IVIG；C.对大剂量IVIG不反应且病情难以控制者。应用方法(application methods) 可考虑与阿司匹林(aspirin)和双嘧达莫（dipyridamole,潘生丁persantine）联合应用常用泼尼松(prednisone)12mg/