Pediatric mucocutaneous lymph node syndrome
Introduction
Introduction to pediatric skin mucosal lymph node syndrome Skin mucosal lymph node syndrome, also known as Kawasaki disease (Kawasakidisease), skin-mucosa-lymph node syndrome (MCLS), is an acute fever and rash disease in children. Its characteristic manifestations are: skin mucosal changes and non-suppurative lymphadenopathy, the course of disease is self-limiting, and a small number of patients may also die suddenly due to coronary artery disease. The disease was first proposed by Kawasaki (1961) and officially reported in 1967, and it was named "acute (toe)-specific desquamation with acute febrile skin mucosal lymph node syndrome." The disease is widely distributed in Japan, and many cases have been reported in China. basic knowledge Sickness ratio: 0.0001% Susceptible people: children Mode of infection: non-infectious Complications: coronary aneurysm coronary heart disease
Cause
Pediatric skin mucosal lymph node syndrome etiology
(1) Causes of the disease
Although many scholars have done a lot of research, the etiology of Kawasaki disease is still unclear, but a large number of epidemiological and clinical observations show that Kawasaki disease is caused by infection, given the fever, rash, and self-limiting disease. Conjunctival hyperemia, cervical lymphadenopathy and predisposition in children, the obvious geographical distribution during the outbreak of the epidemic suggests that the incidence is related to infection.
However, standard and more advanced methods of detection of viruses and bacteria and serological tests are unable to determine the sole cause of microbes, although a number of possible infection factors have been reported, including Epstein-Barr virus, human herpesvirus 6,7 , human parvovirus, Yersinia, but further studies can not confirm that in Japan and the United States, due to the experience of some families washing carpets during the outbreak, the dust mites in the family are also considered The disease factor, which is also accidental, has been considered as a causal factor, including the use of certain drugs, exposure to pets and immune reactions, but not confirmed, on the contrary, for Kawasaki disease Observations in children's immune system have revealed that these children have more serious immune disorders. In the acute phase, the number of active T cells, B cells, and monocytes/macrophages in peripheral blood rises, and there is evidence that lymphatics Activation of cells and monocytes/macrophages is accompanied by an increase in cytotoxic secretion, in addition to the presence of circulating antibodies to the vascular endothelium. Cytotoxic effects.
Therefore, the above observations support the activation of the immune system as one of the pathogenesis of Kawasaki disease. According to the usual degree of immune activation, diseases caused by infection of proteins contained in bacteria and viruses are common features. Proteins act like superantigens (such as staphylococcal toxic shock syndrome toxins, epidermal exfoliative toxins, pyrotoxins of streptococcus), and the hypothesis of superantigens is established. Superantigens differ from general antigens in that they activate Polyclonal B cells promote T cell proliferation and secrete cytotoxins. These effects are directly presented to the histocompatibility complex II (MHCII) by proteins present on the surface of antigen-presenting cells, in response to normal immune responses. In contrast to pre-protein uptake, there is usually a large amount of cytotoxin secreting and promoting the progression of the disease. In the superantigen hypothesis, those super-antigen-like organisms parasitize the gastrointestinal mucosa of susceptible hosts and secrete toxins, sometimes In the pharynx and rectum of children with Kawasaki disease, toxic shock syndrome toxin-1 secreted by Staphylococcus alone can be found, but large The number of experiments were not found, so the superantigen hypothesis yet to be confirmed.
(two) pathogenesis
The main pathological change of Kawasaki disease is vasculitis, and the pathological changes can be divided into four phases:
1. Stage I onset of 0 to 9 days, the main pathological changes for small vasculitis, to the small arterial full-thickness inflammation, common inflammation around the middle and large arteries, at the same time visible whole heart disease, this period is prone to arrhythmia and heart failure, and even heart Source of shock and death.
2. Stage II onset of 10 to 25 days, microvascular inflammation and carditis are relieved in this period, but full-thickness inflammation occurs in the middle artery. The most common coronary artery is aneurysm and thromboembolism, which may be due to severe heart failure and arrhythmia. Myocardial infarction and coronary aneurysm rupture and die.
3. After 28 to 40 days after the onset of stage III, although arteritis and carditis subsided in this stage, the granulation tissue in the middle artery is proliferated, the intima is thickened, and there may be aneurysmal dilatation and thrombosis, which may be due to myocardial infarction. And die.
4. After 40 days of stage IV disease, acute inflammation of the blood vessels completely disappeared, myocardial scar formation, stenosis of the middle artery, calcification, and ischemic heart disease. Kawasaki disease vasculitis is most severe in coronary vessels, mostly occurring in the course of 2 to 3 weeks. According to the frequency of involvement, the left coronary artery trunk, left anterior descending artery, right coronary artery trunk, right circumflex artery, and left circumflex artery are extremely rare. The types of lesions include coronary artery dilatation, coronary aneurysm, coronary artery stenosis or occlusion. Coronary arteritis causes multiple coronary artery dilatation (30% to 50%).
Some of them develop coronary aneurysms, which are the most serious complications of Kawasaki disease. The incidence of coronary aneurysms is 15% to 30% (untreated in the acute phase), which can be single or multiple, and the distal aneurysms are often close to Endoscopic aneurysms coexist, isolated distal aneurysms are extremely rare, coronary aneurysms can be cystic, fusiform or tubular, 58% of aneurysms can gradually subside after acute phase; if coronary aneurysms persist, can develop into coronary Arterial stenosis, occlusion, resulting in ischemic heart disease or myocardial infarction, a small number of tumor rupture, Kawasaki disease complicated with coronary aneurysm risk factors are: male, greater than 1 year; heat course greater than 16 days or repeated fever; white blood cells greater than 30 × 109 / L; ESR greater than 101mm / h; ESR and C-reactive protein increased more than 30 days; ESR and C-reactive protein increased repeatedly; ECG abnormalities, manifested as II, III, aVF lead and / or pre-cardiac Associated abnormal Q wave; signs and symptoms of myocardial infarction, coronary artery stenosis more than 4 to 7 weeks after onset, that is, immediately after the onset of coronary aneurysm, patients with stenosis, the younger the collateral circulation occurs earlier Narrow table Obstructive, segmental stenosis and localized stenosis, the main site of the right coronary artery, followed by left left anterior descending artery, left circumflex artery, coronary artery diameter less than 5mm, more stenotic lesions; diameter greater than 9mm All of them are accompanied by stenotic lesions; the diameter of the aneurysm is greater than 15mm (left coronary artery) or 30mm (right coronary artery), more often associated with stenosis, localized stenosis occurs more than 1 year after onset, with coronary Most patients with arterial stenosis lead to ischemic heart disease, and Kawasaki disease with myocardial infarction accounts for 1% to 2%, which occurs more than 1 year (especially within 1 to 11 months).
The high-risk factors are: the maximum diameter of coronary aneurysm is more than 8mm, the shape of coronary aneurysm is cystic, rosary-like, sausage-like, acute fever lasts for more than 21 days, corticosteroids are used alone in the acute phase, and the onset age is less than 2 years old.
In addition to coronary artery involvement, peripheral arteries (such as radial artery, radial artery, femoral artery, etc.) and organ arteries (such as aorta, mesenteric artery, pulmonary artery, liver, spleen, kidney, brain, gonad, salivary gland, etc.) may also be affected. In addition, it can also cause myocarditis, heart conduction system damage, lymph nodes, liver, gallbladder, etc. are often damaged.
Prevention
Pediatric skin mucosal lymph node syndrome prevention
Nothing too much attention, timely detection of timely treatment.
Complication
Pediatric skin mucosal lymph node syndrome complications Complications coronary aneurysm coronary heart disease
1. Cardiovascular complications Cardiovascular system involvement can cause cardiovascular complications and death, so it is particularly important. Many children suddenly die due to coronary thrombosis, which is more common within 2 to 12 weeks after onset. Japan reported earlier in the 1970s that there was a 1% to 2% case fatality rate, but this figure fell to 0.08% in the 1990s, mainly due to timely diagnosis and appropriate treatment.
(1) Coronary aneurysm: the most serious complication of Kawasaki disease. Nearly 20% to 25% of children have coronary artery malformations, including diffuse dilatation and aneurysms. The expansion of the coronary artery was first discovered on the average 10 days of onset, and the peak of coronary lesions was found after 4 weeks of onset. The aneurysm is cystic or spindle-shaped. Kato and his team have detailed descriptions of the prognosis of coronary aneurysms. Angiography found that 55% of coronary tumors may last 10 to 21 years. 90% of coronary tumors can last for 2 years, but it is still unclear how long a coronary aneurysm can last. Coronary arteries present with endothelial dysfunction, low compliance, and thickening of the vessel wall, and whether these increase the incidence of early atherosclerosis is unclear.
(2) Coronary artery stenosis: Coronary artery stenosis can occur in 42% of children with persistent aneurysms. The most serious type is the occurrence of giant aneurysms (diameter 8 mm). A huge aneurysm does not resolve on its own and can develop into a thrombus, rupture or eventually lead to stenosis. In a long-term survey by Kato et al, 26 of 594 children had a large aneurysm (4.4%). Of the 26 patients, 12 (46%) had coronary stenosis or complete obstruction, and 8 of them had myocardial infarction. The performance of children with myocardial infarction is not typical, can be expressed as nausea, vomiting, pale, sweating, crying, and older children often complain of chest pain or abdominal pain.
(3) Coronary heart disease: some clinical manifestations of fever for more than 6 days, repeated fever between 48h interval, in addition to I° heart block other arrhythmia, less than 1 year old onset, heart enlargement, platelet count, serum white Protein and blood cell counts are low.
(4) Others: In addition to coronary artery involvement, there are other cardiovascular complications. About 50% of children have myocarditis, often showing tachycardia and having an electrocardiogram change. About 25% of patients have exudative pericarditis. About 1% of children have valvular insufficiency and mitral regurgitation. Systemic aneurysms occur in 2% of patients without treatment, and usually these patients also have coronary artery tumors. The most commonly affected arteries are the radial, radial, renal, and mesenteric arteries. However, extensive arterial involvement leads to vasoconstriction, which is rare in peripheral extremities. Unexpected efficacy can be obtained by treatment with prostaglandin E and systemic aspirin and with methylprednisolone (methylprednisolone). Whether there is abnormality in lipid metabolism after Kawasaki disease is inconclusive. Although there is a transient abnormality in lipid metabolism in the acute phase, whether there is a long-term abnormality after onset requires further research to prove. 2. Digestive system damage accounts for about 25%. Lighter patients only have mild digestive tract reaction. Some children may have gallbladder edema. In rare cases, paralytic ileus or intestinal bleeding may occur. Clinically visible vomiting, may be accompanied by bile, generally lasts for 1 to 3 days; diarrhea, 2 to 3 days after the onset of the disease, water, egg-flower soup or bile-like stool, lasting 3 to 7 days, microscopic examination and normal culture; Abdominal pain, bloating and jaundice, electrolyte imbalance and acid-base disorders. Gastrointestinal symptoms can be relieved by themselves or improved as the condition improves. When the liver is swollen, the right upper quadrant is full.
Symptom
Pediatric skin mucosal lymph node syndrome symptoms common symptoms sore throat neck lymph nodes irritability diarrhea lips red uveitis liver function impaired maculopapular hyperthermia meningitis
1. Stage Kawasaki disease is a three-phase disease. The acute phase usually lasts for 1 to 2 weeks. The main features are fever, conjunctival hyperemia, oropharyngeal changes, peripheral extremities, rash, lymphadenitis, aseptic meningitis. , diarrhea and impaired liver function, myocarditis is common in the acute phase, although coronary arteritis also occurs at this time, but the heart ultrasound examination can not detect the presence of aneurysm, when fever, rash and lymphadenitis improved after entering the Asian In the acute phase, at about 1 to 2 weeks after the onset of fever, there is skin and foot peeling and thrombocytosis. In addition, coronary aneurysm begins to form in this period, and the risk of sudden death is the highest. The subacute period lasts until 4 weeks after fever. After 6-8 weeks, when all clinical symptoms disappeared, the erythrocyte sedimentation rate returned to normal and then entered the recovery phase.
2. The main symptoms continue to be high fever is the characteristic of the acute phase. The typical fever is usually acute, the heat is up to 39 °C, and it is a relaxation heat. If it is not treated in time, the high heat can last for 1 to 2 weeks, sometimes up to 3 to 4. Week, on the other hand, if intravenous immunoglobulin and large doses of aspirin are used intravenously, fever often resolves within 1 to 2 days.
Bilateral conjunctival hyperemia often occurs after fever for 24 to 48 hours. Conjunctival hyperemia is more common than sacral conjunctiva, especially in the conjunctiva, generally no secretions, and uvitis can be found in slit lamp examination.
The changes in the oropharynx were also seen 24 to 48 hours after the onset of heat. Initially, the lips were reddish. After a few days, swelling, cleft palate and hemorrhage occurred. The most typical is tongue nipple hyperplasia, ie strawberry tongue, and the mouth and throat are obviously congested, but Not accompanied by ulcers and secretions.
Usually 3 to 5 days after the onset of the disease, the palms and the soles of the feet are red, the hands and feet are hard and swollen. After 10 to 20 days of heat, the hands and feet become hard and swollen and tend to subside. When entering the subacute phase, the ends of the toes begin to peel. In addition, the entire palm and the sole of the foot are involved. One to two months after the onset of Kawasaki disease, a lateral groove (Beau line) can appear on the nail.
The rash can be of many types even in the same patient, and can occur in the limbs at the same time. The rash is more common in the trunk and the proximal end of the extremities. Generally, there are no significant features. The most common are the maculopapular rash, the scarlet fever-like rash and the polymorphic rash. More common, rash in the groin and peeling occurs, all of which occur in the acute phase, which occurs earlier than the nail peeling.
In comparison, other symptoms can be seen in more than 90% of children with Kawasaki disease, and cervical lymphadenitis is only seen in nearly 50% to 70% of children. Lymph node enlargement occurs 1 to 2 days after onset, more common in singles. Side, generally no more than 1.5cm in diameter, soft to touch, but can not be pushed, no suppuration.
3. Accompanying symptoms All symptoms related to Kawasaki disease indicate multiple organ involvement, and all children are irritated. About 25% of children have mononuclear cells in the cerebrospinal fluid, and the protein content is normal or slightly elevated. The sugar content is normal, 1/4 to 1/3 of the children have gastrointestinal manifestations. In the acute phase, the small joints may have arthritis, while the large joints are mostly affected in the second and third weeks after onset. Those with large joint exudative lesions can be treated by joint puncture. In addition to cardiovascular complications, the lesions of other affected organs are self-limiting.
4. Atypical Kawasaki disease Children with fever and other manifestations (less than 4) are called atypical Kawasaki disease, and there is also a risk of complicated coronary aneurysm. Atypical Kawasaki disease occurs mostly in small infants, and These symptoms are not easy to detect. Therefore, Kawasaki disease is also one of the differential diagnosis of persistent fever in infants. In the above cases, Kawasaki disease is mostly diagnosed after coronary aneurysm by echocardiography.
5. Kawasaki disease in older children As mentioned above, Kawasaki disease rarely occurs in children older than 8 years of age, and all of the clinical features of children at this age are not sufficiently obvious. In limited reports, these Children take longer from onset to diagnosis, so they often delay treatment. In addition, some accompanying symptoms such as vomiting, diarrhea, weight loss, sore throat, headache, pseudomeningitis are more common, and more importantly, Older children are more prone to coronary artery malformation. In older children, the age of onset and the timely treatment are important factors in determining the prognosis of cardiovascular complications.
Examine
Examination of pediatric skin mucosal lymph node syndrome
The diagnosis of Kawasaki disease has many typical abnormalities in the laboratory, but there is no specificity. The acute phase markers such as ESR, C-reactive protein, 1-antitrypsin increase after fever and last for 6 to 10 weeks, in acute The total number of white blood cells is normal or elevated, and polymorphonuclear leukocytes are also elevated. There is almost no leukopenia in children with Kawasaki disease. Positive cell anemia is common. The peak of thrombocytosis occurs in the 10 to 20 days of the disease. The enzyme is elevated in the acute phase, and the increase in bilirubin is less common. About one-third of patients have aseptic pyuria in the first week of onset, and can occur intermittently, due to the number of patients with Kawasaki disease. The activation of cloned B cells, so anti-nuclear antibodies and rheumatoid factor can be negative.
1. Chest X-ray examination generally has no clinical significance, and there is an increase in lung texture. A few children have flaky shadows or pleural reactions, and the heart shadow is often slightly enlarged. In children with large aneurysms, chest X-ray examination can only be performed. Late stage suggests calcification of the aneurysm.
2. There is no characteristic change in ECG, only the prolongation of PR interval and QT interval, QRS wave low voltage, no ST-T segment change, ST segment elevation, T wave inversion and pathological Q wave appearance Can be diagnosed as acute myocardial infarction.
3. Echocardiography Two-dimensional echocardiography has been widely used to evaluate ventricular function, blood reflux, pericardial effusion and coronary anatomy. It can better indicate the possible expansion of coronary artery in the acute phase through the trace of cardiac ultrasound baseline. The degree of echocardiography should be repeated in the subacute phase, because this period is a good period of coronary aneurysm, which is the most likely to cause sudden death. In the rehabilitation period, the echocardiography can be used to evaluate the progress of the early malformation. There is no approved range of coronary artery diameters. The experience of the Kawasaki Research Committee in Japan is as follows; in children younger than 5 years of age, the coronary artery diameter > 3 mm can be considered as expansion. The standard of supplementation is: if the diameter of a section of blood vessels is relatively close The blood vessels are 1.5 times larger, and the expansion can be diagnosed. In addition to the diameter, the structure of the coronary arteries is also important. The damaged coronary arteries have irregular blood vessel cavities and wall thicknesses, so that the blood vessels can block the lumen.
4. Coronary angiography is necessary for angiography in patients with myocardial ischemia and multiple coronary hemangioma, but it must be performed after acute recovery in the acute and subacute phases. Coronary artery is not clear for cardiac ultrasound. Stenosis and coronary artery lesions, selective angiography can be clearly seen. Recently, magnetic resonance coronary angiography in a small number of adolescents and young people with Kawasaki disease has been confirmed to diagnose coronary artery tumors, but this technique There are also limitations.
5. Other examination electron beam (ultra-high speed) CT (EBCT) can display the main branches of the coronary artery. The silhouette of the coronary artery can be displayed separately after the silhouette to define the type and location of the coronary aneurysm. Electron beam CT can show Kawasaki disease with coronary artery Arterial stenosis, calcification, calcification can be manifested as small calcification spots (type A), arch calcification (type B) or local stenosis calcification (type C), normal pediatric intravascular ultrasound shows coronary artery as a symmetric circular lumen; blood vessels The wall is smooth, can not show the inner membrane, the middle layer and the outer membrane three-layer structure (adults can show three-layer structure), if the blood vessel wall shows three layers of structure, suggesting endometrial hypertrophy, radionuclide myocardial imaging can show myocardial perfusion, clear Coronary perfusion.
Diagnosis
Diagnosis and diagnosis of cutaneous mucosal lymph node syndrome in children
diagnosis
Diagnostic criteria
Because the cause of Kawasaki disease is not clear, there is no validated diagnostic criteria. The diagnosis of Kawasaki disease mainly depends on clinical standards. These standards were developed by the Kawasaki Research Center in Japan. There are 6 major clinical manifestations of Kawasaki disease, clinical diagnosis. It is necessary to have 5-6 of them at the same time. In the recently revised standard, since many children will have coronary aneurysms faster, only 4 cases can be diagnosed. The American College of Cardiology's diagnostic criteria and This is roughly the same, but there must be a fever for more than 5 days. More and more patients have not been diagnosed with the diagnostic criteria but have been diagnosed with Kawasaki disease because of the above clinical manifestations, and received intravenous immunoglobulin therapy because of the Kawasaki A retrospective study of the disease found that the presence of coronary aneurysms can be diagnosed immediately after acute fever, suggesting that it is inappropriate to use a full diagnostic criteria to confirm the disease.
Diagnosis is usually performed using the revised diagnostic criteria (December 1988) of the 3rd International Kawasaki Conference:
1. Fever lasts for more than 5 days, a few less than 5 days, antibiotic treatment is invalid.
2. Changes in the extremities of the extremities In the acute phase, there are hard swelling of the hands and feet, and there are erythema at the palm () and finger (toe) ends; there is a membrane peeling at the transition of the nail bed skin during the recovery period.
3. rash erythema multiforme, more trunks, no blisters and molting.
4. The conjunctiva of the ball is conjunctival hyperemia.
5. Oral mucosa lip flushing, bayberry tongue, diffuse hyperemia of the oropharynx mucosa.
6. The cervical lymph nodes are non-suppurative and have a diameter greater than 1.5 cm.
Those who meet the above five or more diagnostic criteria can be diagnosed, but other diseases should be excluded, especially Staphylococcus, Streptococcus, Measles and Leptospira infection. For those who meet the above 4 or 3 diagnostic criteria, if in the course of the disease Coronary aneurysm confirmed by echocardiography or coronary angiography (more common in infants under 6 months or older children over 8 years old); or meet the above four diagnostic criteria, but echocardiographic findings of coronary artery wall luminance Enhancement (this type of coronary artery dilatation is rare), can be diagnosed as Kawasaki disease in addition to other infectious diseases (viral infection, hemolytic streptococcal infection, etc.), if the following clinical manifestations contribute to the diagnosis of atypical Kawasaki disease:
1 BCG vaccination reproduces erythema, scrotal swelling, and perianal skin flushing;
2 the number of platelets increased significantly;
3C reactive protein and erythrocyte sedimentation rate increased significantly;
4 echocardiography shows coronary artery dilatation or increased arterial wall luminance;
5 hear heart murmur or pericardial rubbing sound;
6 hypoalbuminemia occurred.
Differential diagnosis
Kawasaki disease has many similar manifestations to other infectious diseases. It needs to be identified with bacterial infections such as scarlet fever, staphylococcal skin symptoms, toxic shock, rheumatic fever, rocky mountain spotted fever and leptospirosis, viral infection. Also identified with Kawasaki disease, including measles, Epstein-Barr virus and adenovirus infections, non-infectious diseases such as Stevens-Johnson syndrome, drug reactions and juvenile rheumatoid arthritis.
1. The pathological changes of infant nodular polyarteritis are similar to those of Kawasaki disease, mainly affecting medium arteries, especially coronary arteries, which can form aneurysms and thrombosis. Clinical fever, rash, conjunctivitis, cervical lymphadenopathy, often die in Heart failure is easily confused with Kawasaki disease, but the disease has very few infants, severe kidney damage, and poor prognosis, while Kawasaki disease is a self-limiting disease with mild renal damage and good prognosis.
2. Exudative erythema multiforme may have fever, rash, eye conjunctivitis and oral damage, but the rash is erythema multiforme with large pieces of peeling, oral ulceration and pseudomembrane formation, conjunctiva has purple blue Secretion, palm () end without flushing, etc., can be distinguished from Kawasaki disease.
3. Juvenile rheumatoid arthritis This disease has fever, rash, swollen lymph nodes, joint damage, finger (toe) joint fusiform swelling, limited mobility and heart damage, should be differentiated from Kawasaki disease, but juvenile rheumatoid Arthritis rash is transient, no swelling of the hands and feet, no flushing at the palm () end, no membranous peeling at the nail bed and skin transition, rheumatoid factor and anti-nuclear antibody positive, etc., can be differentiated from Kawasaki disease.
4. Systemic lupus erythematosus This disease is based on the face, lupus cells can be found in the blood, anti-nuclear antibodies and anti-double-stranded DNA antibodies are positive, and can be distinguished from Kawasaki disease.
5. Infectious diseases Staphylococcus, hemolytic streptococcus, Yersinia, Epstein-Barr virus, Chlamydia, measles, influenza virus, Leptospira and Candida albicans infection, etc., need to be differentiated from Kawasaki disease.
