The most common complication of Kawasaki disease is coronary artery disease. It is not easy to miss diagnosis and misdiagnosis for typical Kawasaki disease, but it is difficult to diagnose incomplete Kawasaki disease. So how to make a better diagnosis? How to treat and follow up? A text for you to understand!
Kawasaki disease is a common autoimmune systemic vasculitis disease in children. It is self limiting and often occurs in children under the age of 5. It can involve small and medium-sized vessels, especially coronary arteries, with coronary artery dilation, stenosis, aneurysm and myocardial infarction. The incidence of coronary artery disease in children without formal treatment is 25% – 30%. After early treatment, The incidence of coronary artery aneurysm can be reduced to 5%. Now I summarize the information about my study of Kawasaki disease, sort it out and share it with you.
For the damage of coronary artery, scholars believe that it may be related to the injury of vascular endothelial cells, the degradation of vascular elastin and vascular wall structure protease and the negative regulation of T cell activation. Vascular endothelial cell injury and fibroblast growth factor 2 (FGF23), neutrophil surface adhesion molecule (CD11b), interleukin-1 β( IL-1 β) And TNF- α Increased expression of IL-1 β The expression of receptor antagonist (IL-1ra) is reduced. Among them, some studies have shown that IL-1 in KD patients who do not respond to gamma globulin treatment β The expression of IL-1 was up-regulated β The expression of receptor antagonist (IL-1ra) decreased; TNF can cause vascular injury and thrombosis, such as TNF in KD mouse model- α And / or tnfr-i (TNF- α Knockout of (receptor) gene did not lead to coronary artery inflammation and coronary aneurysm, which provided a theoretical basis for the treatment of KD cases with gamma globulin tolerance.
Coronary thrombosis may be related to cardiovascular endothelial cell injury, hemodynamic changes and increased blood coagulation. Under the action of various factors, coronary endothelial cell injury and arterial dilation slow down the blood flow and produce eddy currents, increase the contact probability between platelets and injured endothelial cells, and interact with many factors, resulting in thrombosis.
Typical Kawasaki disease has obvious clinical manifestations, such as fever, relaxation fever or residual fever, and ineffective antibiotic treatment; Rash, pleomorphic red macula or urticaria like rash. In the acute stage, the palms and soles can be red and the fingertips can be hard and swollen, and in the recovery stage, there is typical membranous peeling; Conjunctival congestion occurs in both eyes, but there is no purulent secretion, diffuse congestion of oral mucosa, flushing and chapped lips, and red bayberry tongue can be seen; Both neck lymph nodes are swollen, hard and tender, but the surface skin has no typical manifestations such as redness and suppuration. When the heart is involved, the corresponding clinical manifestations can appear.
1,Laboratory examination: blood routine examination includes elevated leukocytes, anemia, elevated platelets, increased ESR and CRP, decreased serum protein, abnormal myocardial enzymes, etc. These examination results can suggest the role of coronary artery damage. Many scholars believe that platelets > 300 × 109 / L, albumin < 35 g / L and CRP > 100 mg / L were related risk factors for coronary artery disease, and the latter two were independent risk factors（ Other risk factors include: male children, age < 11 months or > 48 months, incomplete KD, IVIG resistance, fever days ≥ 10 days.)
2,ECG examination: ST-T wave changes, arrhythmia, myocardial ischemia, myocardial infarction, etc.
3,Chest X-ray: heart enlargement.
4,Color Doppler echocardiography: it is an economical, noninvasive and expensive examination method. It can measure the inner diameter of coronary artery, left ventricular systolic function and the presence of pericardial effusion. It has advantages in the diagnosis of coronary artery diseases. Reference standard for normal value of coronary artery in children in China:
< 3 years old, coronary artery diameter < 2.5 mm;
3 ~ 9 years old, coronary artery diameter < 3.0 mm;
>9 years old, coronary artery diameter < 3.5 mm.
When the coronary artery diameter exceeds the normal value or the diameter of a segment exceeds 1.5 times the diameter of adjacent segments, coronary artery dilatation can be diagnosed to assist in the diagnosis of Kawasaki disease or follow-up of coronary artery damage.
5,Coronary angiography: it is the gold standard for the diagnosis of coronary artery disease, but invasive examination limits its application.
Typical Kawasaki disease
The clinical manifestations of typical Kawasaki disease are relatively clear, and it is generally not easy to miss diagnosis or misdiagnosis. For clinical cases, Kawasaki disease can be diagnosed if fever ≥ 5 days and meets 4 or more of the following 5 items. Kawasaki disease can also be diagnosed if there are less than 4 items, but echocardiography indicates coronary artery dilatation:
(1) The conjunctival membrane of both eyes was congested without purulent secretion;
(2) Chapped lips, diffuse hyperemia of oral mucosa, red bayberry tongue;
(3) Acute non suppurative cervical lymph nodes are large, with a diameter > 1.5 cm.
(4) Changes of hands and feet: redness of palms and soles, hard swelling of fingers (toes) in acute stage, and membranous peeling of fingers (toes) in recovery stage;
(5) Pleomorphic rash.
Incomplete Kawasaki disease
For incomplete Kawasaki disease, clinical diagnosis is difficult, especially due to nonspecific laboratory diagnostic indicators, misdiagnosed as common cold, sepsis, drug allergy and other diseases, delayed treatment opportunity, and the probability of coronary artery damage is also high (delayed treatment opportunity is also one of the reasons), and the prognosis is often not very optimistic. According to the retrieved literature, fever is the most common symptom of incomplete Kawasaki disease. If it is combined with the following situations, it highly suggests that incomplete Kawasaki disease is more likely:
1,Perianal skin flushing and desquamation occur more than fever within 3-5 days.
2,The BCG vaccination site was red and swollen.
3,Finger tip membranous desquamation.
4,Fever is ineffective after anti infective treatment, and other diseases are excluded. The blood vessel wall brightness is enhanced, the coronary artery is not gradually narrowed, the left ventricular systolic function is reduced, and pericardial effusion is excluded. Coronary artery disease in infants occurs early and can occur within 3 days.
5,If the fever exceeds 5 days and the antibiotic treatment is ineffective, but only meets 2-3 items of typical Kawasaki disease diagnostic specimens, pay attention to the laboratory examination results. If the following 3 or more items are met, it can also be diagnosed as incomplete Kawasaki disease and start treatment: leukocyte count in acute phase ≥ 15 × 109 / L, mainly granulocytes, CRP > 3.0 mg / L, ESR > 40 mg / L, albumin ≤ 30 g / L, anemia, elevated transaminase, platelet > 450 7 days after onset × 109 / L, leukocytes ≥ 10 / HP in routine urine.
For children diagnosed with Kawasaki disease, the treatment scheme is as follows:
1,Gamma globulin: the dose is 2 g / kg, intravenous drip. If there is intravenous resistance, the second dose of IVIG will be given. Children who have used Jing C should not be vaccinated against measles, rubella and mumps within 9 months. However, as for the dosage and time, some scholars have questioned this. For example, the incidence of coronary artery damage in children who were given intravenous C prematurely, such as Egami K, is even higher! Premature administration has the risk of increasing c-ball resistance, and too late can not well prevent the damage of coronary artery. Within 5-10 days of the course of disease, the use of jing-c in the treatment of Kawasaki disease has achieved satisfactory results. In terms of dose, for families facing financial difficulties or those who are difficult to raise enough C ball (referring to C ball 2 g / kg), the scheme of IVIG 1 g / kg x 1 or 2 times may also be an option, but it is generally not recommended to use 400 mg / (kg. D) 4-5d.
2,Aspirin: 30 ~ 50 mg / kg • D orally. Aspirin sharply reduced to 3 ~ 5 mg / kg • d after 3 days of heat retreat. The course of treatment is generally 6-8 weeks without coronary artery damage; If there is coronary artery disease, the drug should be taken orally until the coronary artery returns to normal.
3,Other antiplatelet drugs, such as clopidogrel [0.2 mg / (kg • d) combined with 9 mg / (kg • d) aspirin] and dipyridamole [2 ~ 5 mg / (kg • d) combined with aspirin].
4,Anticoagulant drugs: the indications are moderate or above coronary artery dilatation, rapid coronary artery dilatation with thromboid echo, and a history of myocardial infarction. Drugs such as warfarin [0.05 ~ 0.12mg / (kg • d), oral once, INR: 1.5-2.5], low molecular weight heparin [2-3mg / (kg • d), bid] .
5,TNF- α Monoclonal IgG antibody: such as infliximab (5 mg / kg).
6,Glucocorticoids: in 1979, a small observational study reported that patients treated with glucocorticoids had a higher incidence of coronary artery tumors, so steroids have always been regarded as taboo in the treatment of Kawasaki disease and believed that they can promote thrombosis. Recently, a meta-analysis on the early treatment of Kawasaki disease with glucocorticoid showed that glucocorticoid combined with IVIG as the initial treatment showed better protective effect compared with traditional gamma globulin treatment. The early intervention effect was more significant in high-risk patients (IVIG treatment resistant), and it was emphasized that it was the most beneficial when KD was just diagnosed, The results were published in JAMA pediatrics on October 17, 2016.
1,For patients with no coronary artery disease or only transient coronary artery dilatation, physical labor is not limited after discharge. It is recommended to follow up once a year in January, March, June, one year and five years after the onset of the disease, and carry out blood routine, ECG or cardiac color Doppler ultrasound according to the situation of the children.
2,For patients with mild coronary artery dilatation (inner diameter < 4.0 mm) or moderate coronary artery dilatation (4.0 mm < inner diameter < 8.0 mm), limit violent activities, and it is recommended to follow up once a year in January, February, March, June, 1 year and 5 years after onset. The follow-up content is the same as above. For patients with moderate coronary artery dilatation, coronary angiography can be performed if necessary.
3,Children with coronary artery aneurysms (inner diameter > 8 mm) are prohibited from any exercise. They are followed up regularly every month according to their condition. After their condition is stable, they are followed up once every 3 months. In addition to the routine follow-up, those with ischemic signs should undergo selective coronary angiography.