Standard for diagnosis and treatment of the latest Kawasaki disease

Standard for diagnosis and treatment of the latest Kawasaki disease

Mcls of cutaneous mucosal lymph node syndrome (KD of Kawasaki disease)

Cqs disease is an unknown cause of vasculitis syndrome. With young children, clinical characteristics of fever, skin mucosal lesions and lymph node enlargement. Due to the increasing incidence of this disease in recent years, clinical misdiagnosis more, the early treatment of this disease is better.

Cqs disease is not life-threatening, but will die from its complications, usually serious complications are myocardial infarction, the evolution of complications: Early heart failure-→ arrhythmia-→ coronary dilatation-→ later cardiac infarction.

I. Etiology (specific to the following, may not be sufficient basis)

1, Infection: beta-hemolytic lian, EB virus.

2. Immune response: There is an immune disorder in the acute stage, which may be related to the immune mediated by a variety of pathogens caused by certain host infections.

3. Other: Related to drugs, chemical element substances too sensitive.

Ii. pathological changes (four phases)

1, early (1-2 weeks): Systemic small arterial inflammation, visible to the coronary artery outer membrane neutrophils, mononuclear cells invasion, this is the early performance, the most light.

2, Polar period (2-4 weeks): This period is the most dangerous, easy to death, manifested throughout the vasculitis, intracellular membrane invasion, this period after the basic formation of coronary artery tumor, intimal hyperplasia, hypertrophy, after this period basically no aneurysm appeared.

3, Granuloma stage (4-7 weeks): vascular inflammation subsided, intimal granulation tissue hyperplasia, intimal hypertrophy further.

4, the old period (7 weeks-4 years): Scar formation, blood vessels are mostly coronary stenosis, prone to thrombosis-→ causes myocardial infarction is the main cause of death of Cqs disease, another can cause aneurysm rupture (stenosis-→ heart compensatory contraction-→ arterial wall pressure increased-→ aneurysm rupture)

Third, clinical manifestations

The onset age is 1 months ~13. 8 years old, average 2.6 years old, median age 2. 0 years old. Peak onset age is 1 years old, 87% children <5 years old, 79% children <4 years old, 67% children <3 years old, 49% children <2 years old, 21% children <1 years old. Male 716, female 391, male: female =1. 83:1, course 1-67 days, average 6-7 days. There are popular years and seasonal distribution characteristics, spring and summer more see, in addition to the main performance, some children appear BCG vaccination site redness, peeling around the anus and other manifestations, but these performance than 6 main symptoms are rare, and mainly appear in children under 3 years of age, The diagnosis of atypical KD in infants is helpful for Beijing children Kawasaki Disease Cooperative Group Fever is still the most common clinical manifestation, and the multi-form rash replaces the lymph node large becomes the most rare clinical characteristic. (Beijing pediatric Kawasaki Disease Collaboration Group)

(i) Main symptoms and signs

1, Fever: 38-40 ℃ is missed hot, lasts 1-2 weeks. Like SARS must have fever, and fever for more than 5 days, antibiotic treatment ineffective.

2. Skin Mucosa:

(1) Rash: to the heart, polymorphism, the same period may have several rash, such as urticaria-like, measles-like, deep red, scarlet fever-like rash, but no herpes.

(2) Limb changes: Refers to (toe) is a spindle-shaped swelling, joint pain, stiffness (similar to the manifestation of rheumatoid facet lesions), hand-foot hard edema (compression is hard), the above is the Fever period. When the body temperature is back, the limb anus Zhou block peeling.

(3) Mucous membranes

① bulbar conjunctival congestion: For dry inflammation, no tears, secretion can be identified with conjunctivitis.

② mouth chapped, chapped: Visible to the blood scab (lip dry color red).

③ Mouth Diffuse congestion: visible Coriolis spots (identified with the measles), a fresh beef color.

④ tongue nipple protrusion: yangmei tongue. (i.e., swelling of the tongue nipple, redness resembling a strawberry, often in scarlet fever)

3. Lymph node enlargement: to the neck, one side of the neck more see, no pain, no fever, simple swelling, can be identified with acute lymph nodes.

(ii) Cardiovascular symptoms

1, heart inflammation: can have myocarditis, endocarditis, symptoms of pericarditis, signs, no specificity. It can be manifested as irregular rhythm, heart failure, murmur, distant sounds and other changes, often appearing in acute fever.

2, cardiovascular: mainly damage the coronary arteries, early may have systolic murmur, rhythm changes.

① coronary inflammation: The incidence rate is 50%, does not appear the expansion, only inflammation manifestation, lightest.

② Coronary artery tumor: The 12th day began to expand, 8 weeks the most obvious, the acute period of high incidence, after the acute period basically does not appear, manifested as coronary artery dilatation is greater than 3mm.

③ coronary stenosis: Seen in phase fourth, scar formation, manifested as myocardial ischemia, cardiac infarction, angina pectoris.

Risk factors of coronary artery aneurysm complicated with myocardial infarction

1, the maximum diameter of coronary artery tumor >8mm above

2, coronary artery tumor morphology is cystic, Candida, sausage-like

3. Fever lasts more than 21 days in acute period

4. Use of corticosteroids alone in the acute phase

5. The age of onset is under 2 years

Clinical features:

1, more in the rest, quiet or sleep suddenly occurred (accounted for 63%)

2, many manifestations of shock, strong crying, chest pain, abdominal pain, vomiting and other gastrointestinal symptoms, the baby complained of chest pain less (may be related to age), may also show dyspnea, heart failure, arrhythmia;

3, asymptomatic people accounted for a large proportion (accounted for 77%,73/95), this is the characteristics of Cqs disease complicated with myocardial infarction;

4. The prognosis of myocardial infarction is related to the number of re-infarction and the location of coronary artery obstruction.

(iii) Other systems

1, urinary system: pus urine, urine protein;

2, digestive system: liver function changes;

3, Brain: aseptic encephalitis.

IV. Laboratory Inspection

1, Blood: early white blood cells up to 20, platelets normal, but in 2 weeks after can increase to more than 30; Increased ESR, CRP (C-reactive protein) increased, anti-o normal.

2, Heart: two-dimensional color echocardiography shows coronary artery dilatation or coronary artery tumor.

(1) Abnormal Q-wave q/r proportional >0.3qs waveform

(2) normal inner diameter of coronary artery: 4 weeks-3 years old to 2.5mm,3-9 years old for 3mm,9-14 years for 3.5mm. Coronary dilatation refers to the ratio of the inner diameter greater than the normal range or the >0.3 of the coronary artery to the aortic root.

(3) Coronary artery dilatation classification: 0 levels: normal range, Level 1: <4.0mm;2 level: 4-7mm, this level is the most common; Level 3: ≥>6mm or spherical, spindle-like changes.

V. Diagnostic criteria

1, fever more than 5 days;

2, hand and foot symptoms: the end spindle-shaped swelling, hot peeling;

3. Skin-shaped erythema;

4, mucosal changes: oral mucosa beef color, bulbar conjunctival congestion;

5, mouth chapped lips, Yangmei tongue;

6, non-purulent cervical lymphadenitis.

Including fever in a total of 5, without laboratory support can be diagnosed, if there is a B-tip coronary artery changes, including fever in a total of 4, but at this time to rule out other diseases: such as wind and dampness (resistance o increase). 6 articles can be summarized as: fever, skin mucosa, lymph nodes, tongue, hand and foot.

Early diagnosis of incomplete Kawasaki disease

　　Typical Kawasaki disease refers to unexplained fever of more than 5d, and has 5 other major clinical characteristics of 4 or more than 4. But the incomplete Kawasaki disease is refers to the fever above 5d, other main clinical manifestation only conforms to 3 or 2, but the echocardiography confirmed has the coronary artery (short-term coronary arteries) pathological changes. The diagnosis of incomplete Kawasaki disease is divided into two cases: (1) If the echocardiography shows the coronary artery or coronary artery moderate expansion, can be diagnosed as CQS disease, to give intravenous immunoglobulin (IVIG) treatment, (2) if the coronary artery mild dilation or coronary wall enhancement, vascular cavity morphology abnormalities or left ventricular segmental motion abnormalities ( It is suggested that local myocardial ischemia is CQS disease, and the same is given to IVIG treatment. The above-mentioned incomplete Kawasaki disease diagnosis with coronary lesions as a necessary condition, although effectively avoid the expansion of Kawasaki disease clinical diagnosis, but also caused partial incomplete Kawasaki disease missed diagnosis. Because in the acute stage of Cqs disease, the coronary vein of coronary artery is dilated and is rare. More than half of children with Kawasaki disease had no significant changes in the morphology of the coronary arteries during the course of the disease. In addition, Kawasaki disease lacks diagnostic clinical features and specific laboratory tests, and the main clinical manifestations are not present at the same time of the course, so the early diagnosis of incomplete Kawasaki disease is difficult. In recent years, through the epidemiological analysis of confirmed cases, the following clinical and laboratory features contribute to the early diagnosis of incomplete Kawasaki disease. Clinical features:(1) incomplete Kawasaki disease in <6 months of infants more see. A small number of infants clinically only showed fever. For <6 months, fever sustained more than 7d, at the same time there are systemic inflammation of the laboratory indicators and can not be explained with other febrile diseases, should do echocardiography examination; (2) "irritability", that can not appease the irritability, crying disturbed. This "irritability" phenomenon is more prominent than other inflammatory diseases; (3) Some features of the main clinical manifestations: the enlargement of cervical lymph nodes is limited to the front of the thoracic lock mastoid muscle. When the Bulbar conjunctiva is congested, there is a ring-free area around the iris. The oral mucosa can be highly congested but rarely ulcer, (4) The BCG site reproduces erythema sclerosis, (5) Acute scrotal and/or inguinal skin Flushing, subacute stage scrotal and (or) groin peeling, (6) urethral congestion, (7) may have a mild iris ciliary body or anterior uveitis ( Visible anterior chamber floating fine floc under slit lamp);(8) A heart murmur, pericardial effusion or congestive heart failure that could not be explained in the course of the disease, and (9) the presence of a medium aneurysm (non-coronary) in other areas. Laboratory points: (1) C-reactive protein (CRP) significantly increased >30m g/L, (2) erythrocyte sedimentation rate (ESR) significantly increased >40m m/h; (3) The platelet count increased significantly after 7d, which was a typical laboratory feature of Cqs Disease; (4) In the acute period, white blood cell count was increased by miscellaneous x 109/l, with mature and immature granular cells as the main; (5) Unclear causes of povertyBlood, (6) low albumin, ≤30 g/L, (7) Increased serum alanine transaminase and aspartic acid transaminase, (8) sterile purulent urine, urine WBC count ≥10/high magnification field of view. The characteristics of laboratory examination of incomplete Kawasaki disease are similar to those of typical Kawasaki disease. The above laboratory indicators, although non-specific, are helpful in identifying and excluding suspected children. For example, after the onset of 7d, platelet count and ESR,CR p are normal children, Cqs disease is not likely, the recent American Heart Association experts proposed a new guidance rule to help clinicians diagnose incomplete Kawasaki disease: Children unexplained fever >5 D, Only according to 2 or 3 Kawasaki disease main clinical characteristics, should be vigilant against the possibility of incomplete Kawasaki disease. First observe CRP and ESR changes, if crp≥30mg/l,esr≥40 mm/h, plus more than 3 other laboratory indicators (such as the above) in line with the characteristics of Cqs disease, can be diagnosed incomplete Kawasaki disease, need to do echocardiography examination, and give IVIG treatment. If other laboratory indicators are <3, the first line of Echocardiography is examined. Echocardiography showed that coronary lesions were diagnosed as incomplete Kawasaki disease and given IVIG treatment. Echocardiography did not show coronary lesions and still fever, repeated echocardiography examination. If it is self-cooling, Kawasaki disease is unlikely. If the laboratory examines CRP <30m g/l,es r<40m m/h, it should be clinically closely observed to detect CRP changes daily. If the finger end of the fever after the typical peeling, clinical is to be diagnosed as incomplete Kawasaki disease, the echocardiography should be examined to determine whether there is no coronary dilatation. Kawasaki disease can be ruled out if there is no typical finger tip peeling at the back of the heat. For those with unexplained fever above 5d, and with any one of the main clinical manifestations of Kawasaki disease, children should be diagnosed with CQS disease.

High-risk children with coronary artery tumors (KD program in Japan)

1. White blood cell >12;

2. Platelet >350;

3, CRP strong positive;

4, Hematocrit <0.35;< span= "" >

5. Plasma albumin <35g/l;

6, age ≤ 12 months;

7, male.

Illness within 7 days scoring greater than 4 is divided into Ivgg indications

Vi. Treatment

Objective to control systemic vascular inflammation, prevent the formation of coronary artery tumor and thrombotic obstruction.

1, Aspirin: The first week of the onset of drug delivery than in the subsequent incidence of aneurysm to decline, but the need for a larger dose: daily 30-50mg/kg, or even reach daily 50-100mg/kg, commonly used the former dosage, generally used to heat back to reduce the amount to 5MG/KG.D meal, the continued use of medication until the symptoms subside, rash, Hand and foot, ESR Normal, usually need 1-3 months.

2, C Globulin: Intravenous use, 10 days with the best effect. As with aspirin, the incidence of aneurysms can be significantly reduced, the earlier the better, the mechanism: GG closed the blood mononuclear cells, platelets or vascular endothelial cells on the surface of the IGFC and IGFC receptor immune response; GG can make anti-unique antibody (Idiotype) repair (antigen into the body resulting in the production of specific antibodies, when reached a certain amount will cause anti-IG molecule unique immune response of the stable balance) to provide a specific antibody, neutralizing antigen (toxin) effect

GG inhibits the activation of PDGF (platelet-derived growth factor)-PDGF receptor pathway. The American Heart Association (AHA) has suggested that all children with Kawasaki disease use IVGG Therapy. Japan Kawasaki Disease Research Group IVGG Therapy Indications: high-risk patients with coronary artery tumors. At present, our country advocates early (within 7 days of onset) application. The effect of IVGG therapy: Aspirin group alone, the incidence of acute coronary artery enlargement lesions was 35%~45%; aspirin and Ivgg were in the same group, the incidence was 15%~25%. Those who have formed coronary artery tumors, the use of Ivgg group aneurysm withdrawal has a tendency to be earlier than aspirin alone group.

There are several uses:

① classical usage, that is, theoretical usage: 400mg/kg.d/days;

② Large dosage method: 1.0g/kg.d/days, this method is most commonly used in clinical, the most economical, generally the first day after the Fever;

③ Extra-Large dosage method: 2.0g/kg.d/days, this method to the onset of 5-7 days of patients, with this dose can quickly control acute inflammation.

The above several uses, especially the high dosage usage, should pay attention to the speed, especially should observe closely in 30 minutes, attention has the unintentional insufficiency and the allergic reaction.

Ivgg Non-responders (nonresponders, drug resistant) large doses of ivgg in the treatment of KD after fever (>38℃) lasted for 48 hours.

KD Determination of high-dose ivgg resistance:

1, the Fever does not return (>38℃)

2, CRP does not decline

3. White blood cell count (especially neutrophils) does not decrease

4, plasma albumin reduction (especially <30g/l)

5. No decrease in platelet count

6, Blood fdp-e/d two poly and β2-micro-globulin does not decline

7. UCG: Enhancement of coronary artery brightness

Another: The treatment of Cqs disease without reaction to IVIG treatment (Chinese paediatric KD topic)

In the early stage of Cqs disease, after giving IVIg treatment, 36h fever (body temperature > 389C) or 217 D after fever was reproduced and accompanied by at least one of the main clinical features of Kawasaki disease, known as IVIG non-reactive type. About 10% of cases are of this type. IVIg treatment without reaction is a high risk factor for coronary artery tumors. The following disposal is recommended for IVIG treatment: (1) Additional IVIg 112 g/kg, one intravenous drip, and (2) If fever is still not returned, use GCS for treatment. Commonly used methylprednisolone shock treatment, dosage of 20,130 mg/(kg), one intravenous drip, with 113 D (depending on the condition of the Fever). Then instead prednisone 2mg/(KG/D), divided orally. After the normal level of serum CRP was reviewed, it was reduced to 1 mg/(KG/D) and gradually reduced to discontinuation in two weeks. or Methylprednisolone 2 mg/(kg/d), divided into 3 times static note. After the Heat retreat and CRP improved, Methylprednisolone was changed to oral, gradually reduced the amount of drug withdrawal. can also direct oral prednisone treatment, dose 1-2mg/(K g Jesus), heat back gradually reduced amount of medication for 416 weeks. GCS therapy can aggravate the state of blood coagulation and must be combined with aspirin. Heparin-anticoagulant parallel echocardiography and blood pressure tests are recommended for high-dose GCS shock therapy. If there is already a coronary tumor, it is recommended to use a small dose of methylprednisolone or oral prednisone treatment; (3) If the GC is applied. Treatment of fever is still non-refundable, can be added with Ulinastatin (neutrophil elastase inhibitor) or tumor necrosis factor. (tnf-a) monoclonal antibody (infiximab) and other specific inflammatory cytokines antibody therapy. The common dosage of Ulinastatin was 5000u/kg, slow intravenous injection, 316 times a day, with 113 d.

3, other: ①VITE:20-30MG/KG.D; ② dipyridamole (Double Midamo): 3-5mg/kg.d;③ corticosteroids: Using it has double-sided, the front is to reduce inflammation, reduce coronary lesions, negative is there is thrombosis, obstruction of coronary artery recovery. It is mainly used in the early period of high fever, should not be noticed when using, should not be used alone, with the aspirin. ④ has myocardial damage can be added with Atp,co-a and other adjuvant therapy. The above-mentioned drugs are mainly used in the extended period of coronary artery dilatation with aspirin to the inner diameter of the coronary vein <3mm. < span= "" >

Cqs disease can be used for glucocorticoid (GCS) problems

GCS is no longer a taboo for treatment of Kawasaki disease. Recently, many literatures have reported that GCs combined with aspirin to treat Kawasaki disease can shorten the course of disease and help prevent coronary lesions, but the lack of large-sample randomized double-blind research data. At present, a more consistent view of GCS is generally not used as the first choice for the treatment of Kawasaki disease. If the combination of more severe cardiac dysfunction, or the inability to obtain large doses of immunoglobulin, and the IVIg treatment is not responsive and the condition is difficult to control, you may consider the combination of aspirin and double-cha-ta (dipyridamole) combined application. The new method of treating Kawasaki disease is actively being explored due to the high price of IVIg and the inability to prevent coronary lesions completely and effectively. At present, a multi-center randomized double-blind clinical study in the United States will provide more information for the effectiveness of GCS in the treatment of Kawasaki disease.

4, by the above treatment to follow-up six months to one year, there is a long-term coronary expansion of the follow-up, every six months to one year to do an echocardiogram until the recovery of coronary artery expansion

Standard for diagnosis and treatment of the latest Kawasaki disease