Written by Lamon Melania
DEFINITION
Kawasaki syndrome is an acute, febrile, self-limited, infectious, multisystem vasculitis of the middl-sized arteries which occurs in young children.
EPIDEMIOLOGY
It has a peak incidence between 1 and 2 years of age(< 5 years). The disease is rare in children older than 8 years old, and it is uncommon before 3 months of age.Boys are affected more often than girls by a ratio of 1.5 to 1. Japanese and Korean children are at greatest risk (145 per 100,000).The rate for European children is 9 per 100,000, and the rate for African children is 20 per 100,000
SYMPTOMS
Kawasaki Syndrome is characterized by:
- Fever (greater than 39°C that normally lasts for more than 5 days if left untreated)
- Polymorphous skin eruption on trunk
- Conjunctivitis (Bilateral Conjunctival injection)
- Acute Cervical Lymphadenopathy (>1.5 cm)
- Changes in hands and feet (Edema and Desquamation of fingertips)
- Mucus mebrane changes (Dry, red, fissured, or vertically cracked lips) 
DIAGNOSIS
No single test can detect Kawasaki disease,so diagnosis is clinical.
It requires fever and 4 other criteria:skin eruption,Conjunctivitis,Cervical Lymphadenopathy,Changes in hands and feet,Mucus mebrane changes.
Laboratory tests:
-Neutrophils leukocytosis
-Increase VES and PCR
-Thrombocyrtosis(platelets begin to increase from the second week) PubMed:Platelet vascular endothelial growth factor is a useful predictor for prognosis in Kawasaki Syndrome
TPO contributes to thrombocytosis in KD in conjunction with IL-6 and TPO production may be enhanced during the acute phase. PubMed:Elevation of serum thrombopoietin precedes thrombocytosis in Kawasaki disease
-increase D-Dimer
- Significantly decrease fibrinolytic response due to decreased tissue plasminogen activator. In addition increase plasma concentrations of plasminogen and fibrinogen. PubMed:Fibrinolytic response to venous occlusion is decreased in patients after Kawasaki disease
-Liver function tests may show evidence of hepatic inflammation and low serum albumin
-pyuria and proteinuria
Other tests
-Electrocardiogram may show evidence of ventricular dysfunction or, occasionally, arrhythmia due to myocarditis
-Echocardiogram may show subtle coronary artery changes or, later, true aneurysms.
PATHOGENESIS
The etiology is so far unknown. . It is probably caused by an infectious agent,that it acts on subjects genetically predisposed to thrombosis. Infectious disease caused by bacteria or bacterial superantigens (particularly Streptococcus pyogenes) and/or virus(Researchers have focused their attention on a retrovirus type of virus that can promote the type of white blood cell growth seen in the syndrome and on Epstein-Barr virus)
Previous studies have demonstrated that this illness is associated with marked activation of monocyte/macrophages and the selective expansion of Vβ2- and, less so, of Vβ8.1/8.2-expressing T cells in the peripheral blood from Kawasaki syndrome patients during the acute phase of their illness.
These immunologic features are characteristic of diseases that are caused by bacterial toxins which act as superantigens. Staphylococcal enterotoxins and streptococcal exotoxins are prototypic superantigens which stimulate large populations of T cells expressing particular T-cell receptor β-chain variable (Vβ) gene segments. Using the Vβ2+ T-cell expansion as an immunologic footprint for a superantigen, we have extended these observations to the identification and isolation of a novel clone of toxic shock syndrome toxin-1-producing Staphylococcus aureus in the majority of patients with Kawasaki syndrome and streptococcal pyrogenic exotoxin B/streptococcal pyrogenic exotoxin C-producing streptococci in a minority of Kawasaki syndrome patients. Toxic shock syndrome toxin-1, streptococcal pyrogenic exotoxin B, and streptococcal pyrogenic exotoxin C are known to stimulate Vβ2+ T cells. These observations support the hypothesis that the activation of Vβ2+ T cells during the acute phase of Kawasaki syndrome is caused by bacterial superantigen(s).
Recent immunohistochemical findings suggest that many vascular growth factors then play a role in the formation of the coronary artery lesions. The activated suppressor/cytotoxic T cells increase, and the CD8+ suppressor T cells decrease. Serum levels of interleukin (IL)–1, tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and IL-6 are elevated. Involvement of the coronary vessels mimics infantile polyarteritis nodosa, but antibody profiles differ.
Most of the pathology of the disease is induced by a medium vessel arterial vasculitis. Initially, neutrophils are present in great numbers, but the infiltrate rapidly switches to mononuclear cells, T lymphocytes, and immunoglobulin A (IgA)–producing plasma cells. Inflammation involves all 3 layers of vessels. Eosinophils are preferentially accumulated in microvessels
HLA-E and HLA-G gene polymorphism may play a role in the pathogenesis of KD PubMed:HLA-E gene polymorphism associated with susceptibility to Kawasaki disease and formation of coronary artery aneurysms PubMed:Genetic variants in the HLA-G region are associated with Kawasaki disease
Kawasaki disease and soy: potential role for isoflavone interaction with Fcγ receptors, 2013
Kawasaki disease is a diffuse vasculitis occurring in children and showing predilection for the coronary arteries. Differences in diet between Asians and Westerners are touted as reasons for certain ethnic-related discrepancies in susceptibility to cardiovascular disease and cancer in adults. Surprisingly, these cultural dietary differences have not been previously considered as the source of the discrepancy in KD incidence among these ethnic populations. Recent data from genetic studies have highlighted the role of specific immune receptors in the pathogenesis of KD. Functions of the Fcγ receptors (FcGRs) are modulated by isoflavones in soy, in particular, genistein. Epidemiological data from Hawaiian populations support an association between soy consumption and KD. These observations form the basis of a hypothesis: isoflavones participate in KD pathogenesis by modulating function of the FcGRs and by disrupting the balance between activation and inhibition of the inflammatory response.
The relationship between Kawasaki disease (KD) incidence for children <5 y (boxes) or <18 y (diamonds) and adult soy consumption per day for three major ethnic groups in Hawaii (Caucasian in white, Native Hawaiian in gray, and Japanese…
OVID:HLA-E
OVID:HLA-G
WIKIPEDIA:HLA
OMIM:Kasawaki Syndrome and molecular genetics
Association with CD40LG:
After screening the entire CD40LG gene and identifying 22 single-nucleotide polymorphisms (SNPs), performed an association study with 427 Japanese Kawasaki disease patients and 476 healthy Japanese controls. A SNP in intron 4 that was marginally overrepresented in Kawasaki disease patients was found to be significantly more frequent in male Kawasaki disease patients with coronary artery lesions compared to controls (OR, 2.0; 95% CI, 1.07-3.66; p = 0.030). This SNP was extremely rare in a control Caucasian population (0.7%) suggested that CD40LG has a role in the pathogenesis of coronary artery lesions and that this might explain the excess of males affected with Kawasaki disease.
Association with ITPKC:
Onouchi et al. (2007) conducted an affected sib pair analysis of Kawasaki disease that demonstrated linkage to several chromosomal regions, including chromosome 19q13. Onouchi et al. (2008) reported results of linkage disequilibrium (LD) mapping carried out on 19q13.2, through which they identified a functional SNP in intron 1 of ITPKC that was significantly associated with risk of Kawasaki disease and the formation of coronary artery aneurysms in both Japanese and U.S. children. The functional SNP was located in intron 1 of the ITTKC gene. Transfection experiments showed that the C allele of the SNP reduces splicing efficiency of the ITPKC mRNA. ITPKC acts as a negative regulator of T-cell activation through the Ca(2+)/NFAT signaling pathway; the C allele may contribute to immune hyperreactivity in Kawasaki disease.
PATIENT RISK FACTORS
- genetically predisposed to thrombosi
- Infectious disease(Probably:EBV, Bacterial toxin–mediated superantigens ,Parvovirus B19,Meningococcal septicemia,Coxiella burnetii ,HIV, Mycoplasma pneumoniae ,Adenovirus,Parainfluenza type 3 virus)
- Genetic disposition: individuals of Japanese descent, no matter where they live in the world, are more likely to get the disease. An existing history of the disease within a family makes it more likely another family member will get it.
- Abnormality of the immune system.
THERAPY
Treatment should begin as soon as possible, ideally within 10 days of when the fever begins. Usually, a child is treated with gamma globulin (2g/kg iv) and Aspirin (80-100 mg/kg/die) until 48-72 h.after patient has become afebrile.Then only Aspirin until standardization of laboratory(usually within eight weeks).
OVID:the anti-inflammatory effect of gamma globulin therapy
COMPLICATIONS
Coronary Aneurysms may lead to myocardial infarction and death
Patients with Kawasaki syndrome will recover completely, but about 1-2% will die as a result of blood clots forming in the coronary arteries or as a result of a heart attack. Deaths are sudden and unpredictable. Almost 95% of fatalities occur within six months of infection, but some have been reported as long as 10 years afterward. Long-term follow-up of patients with aneurysms indicates that about half show some healing of the aneurysm. The remaining half has a high risk of heart complications in later life.
