A multicenter prospective randomized trial of corticosteroids in primary therapy for Kawasaki disease: Clinical course and coronary artery outcome

Department of Pediatrics and Developmental Medicine, Gunma University Graduate School of Medicine, 3-29-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
Journal of Pediatrics (Impact Factor: 3.79). 10/2006; 149(3):336-341. DOI: 10.1016/j.jpeds.2006.05.025
Source: PubMed


To investigate the role of corticosteroids in the initial treatment of Kawasaki disease (KD).
Between September 2000 and March 2005, we randomly assigned 178 KD patients from 12 hospitals to either an intravenous immunoglobulin (IVIG) group (n = 88; 1 g/kg for 2 consecutive days) or an IVIG plus corticosteroid (IVIG+PSL) group (n = 90). The primary endpoint was coronary artery abnormality (CAA) before a 1-month echocardiographic assessment. Secondary endpoints included duration of fever, time to normalization of serum C-reactive protein (CRP), and initial treatment failure requiring additional therapy. Analyses were based on intention to treat.
Baseline characteristics of groups were similar. Fewer IVIG+PSL patients than IVIG patients had a CAA before 1 month (2.2% vs 11.4%; P = .017). The duration of fever was shorter (P < .001) and CRP decreased more rapidly in the IVIG+PSL group than in the IVIG group (P = .001). Moreover, initial treatment failure was less frequent (5.6% vs 18.2%; P = .010) in the IVIG+PSL group. All patients assigned to the IVIG+PSL group completed treatment without major side effects.
A combination of corticosteroids and IVIG improved clinical course and coronary artery outcome without causing untoward effects in children with acute KD.

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    • "This form of initial treatment significantly reduced the incidence of coronary artery aneurysms. In sequential studies of oral prednisolone plus IVIG therapy as a primary regimen in KD patients, Inoue, et al.26 reported that this treatment regimen improved the overall clinical course and outcomes of CAL without any adverse effects in acute KD. However, the rate of recurrence in the group treated with a combination of oral prednisolone plus IVIG was increased compared to the standard IVIG treated group (4.4% vs. 2.2%, p=0.682). "
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    ABSTRACT: Purpose To investigate the clinical effects of a single high dose intravenous immunoglobulin (IVIG) combined with initial dexamethasone as a primary treatment on Kawasaki disease (KD). Materials and Methods Between January 2008 and December 2010, we reviewed the medical records of 216 patients with complete KD patients that were admitted to a single medical center. 106 patients were treated with a single high dose of IVIG (2 g/kg) alone and 110 patients received IVIG and dexamethasone (0.3 mg/kg per day for three days). Results The combined IVIG plus dexamethasone patient group had a significantly shorter febrile period and duration of hospital stay (1.4±0.7 days vs. 2.0±1.2 days, p<0.001; 5.8±1.7 days vs. 6.9±2.5 days, p<0.001, respectively) than the IVIG alone group. The combined IVIG plus dexamethasone group required IVIG retreatment significantly less than the IVIG only group (12.7% vs. 32%, p=0.003). After completion of the initial IVIG, C-reactive protein levels in the combined IVIG plus dexamethasone group were significantly lower than those in the IVIG only group (2.7±4.0 mg/dL vs. 4.6±8.7 mg/dL, p=0.03). In the combined IVIG plus dexamethasone group, the incidence of coronary artery lesions tended to be lower without worse outcomes at admission after initial infusion of IVIG and in follow-up at two months; however, the differences were not significant (8.2% vs. 11.3%, p=0.22; 0.9% vs. 2.8%, p=0.29). Conclusion Initial combined therapy with dexamethasone and a single high-dose of IVIG resulted in an improved clinical course, in particular a shorter febrile period, less IVIG retreatment, and shorter hospital stay without worse coronary outcomes.
    Yonsei Medical Journal 09/2014; 55(5):1260-6. DOI:10.3349/ymj.2014.55.5.1260 · 1.29 Impact Factor
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    • "KD probably represents an aberrant inflammatory host response to one or more as yet unidentified pathogen(s), occurring in genetically predisposed individuals.2 4 5 KD is associated with systemic vasculitis particularly affecting the coronary arteries, causing coronary artery aneurysms (CAA) in 15–25% of untreated patients while 2–3% of untreated cases die as a result of coronary vasculitis.6–9 In view of the frequency and severity of coronary artery complications, there has been intense interest in treatments to reduce the risk of CAA.6 10–14 KD is also potentially an important cause of long-term cardiac disease in adult life.6 7 Notably, as more children with KD are advancing into adulthood, further studies are needed to (1) improve our understanding of long-term cardiac sequelae, (2) optimise therapy in childhood to minimise risks in adulthood and to ensure the continuation of quality, evidence-based care for KD patients as they transit to adult services. "
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    ABSTRACT: Kawasaki disease (KD) is an acute self-limiting inflammatory disorder, associated with vasculitis, affecting predominantly medium-sized arteries, particularly the coronary arteries. In developed countries KD is the commonest cause of acquired heart disease in childhood. The aetiology of KD remains unknown, and it is currently believed that one or more as yet unidentified infectious agents induce an intense inflammatory host response in genetically susceptible individuals. Genetic studies have identified several susceptibility genes for KD and its sequelae in different ethnic populations, including FCGR2A, CD40, ITPKC, FAM167A-BLK and CASP3, as well as genes influencing response to intravenous immunoglobulin (IVIG) and aneurysm formation such as FCGR3B, and transforming growth factor (TGF) β pathway genes. IVIG and aspirin are effective therapeutically, but recent clinical trials and meta-analyses have demonstrated that the addition of corticosteroids to IVIG is beneficial for the prevention of coronary artery aneurysms (CAA) in severe cases with highest risk of IVIG resistance. Outside of Japan, however, clinical scores to predict IVIG resistance perform suboptimally. Furthermore, the evidence base does not provide clear guidance on which corticosteroid regimen is most effective. Other therapies, including anti-TNFα, could also have a role for IVIG-resistant KD. Irrespective of these caveats, it is clear that therapy that reduces inflammation in acute KD, improves outcome. This paper summarises recent advances in the understanding of KD pathogenesis and therapeutics, and provides an approach for managing KD patients in the UK in the light of these advances.
    Archives of Disease in Childhood 10/2013; 99(1). DOI:10.1136/archdischild-2012-302841 · 2.90 Impact Factor
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    • "Nevertheless, a study found that corticosteroid included in an aspirin-containing regimen reduced the occurrence of coronary aneurysm formation in KD [41]. Recent clinical studies have reported that IVIG combined with prednisolone for the initial treatment of acute KD decreased the incidence of coronary artery involvement [14, 42, 43]. In our study, methylprednisolone treatment suppressed the expression of cytokines such as IL-17 and KC at 2 weeks, but eventually failed to exert a significant effect on the evolution of vasculitis. "
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    ABSTRACT: Coronary arteritis, a complication of Kawasaki disease (KD), can be refractory to immunoglobulin (IVIG) treatment. To determine the most effective alternative therapy, we compared the efficacy of different agents in a mouse model of KD. Vasculitis was induced by injection of Candida albicans water-soluble fractions (CAWS) into a DBA/2 mouse, followed by administration of IVIG, etanercept, methylprednisolone (MP), and cyclosporine-A (CsA). At 2 and 4 weeks, the mice were sacrificed, and plasma cytokines and chemokines were measured. CAWS injection induced active inflammation in the aortic root and coronary arteries. At 2 weeks, the vasculitis was reduced only by etanercept, and this effect persisted for the subsequent 2 weeks. At 4 weeks, IVIG and CsA also attenuated the inflammation, but the effect of etanercept was more significant. MP exerted no apparent effect at 2 or 4 weeks. The suppressive effect exerted by etanercept on cytokines, such as interleukin- (IL-)6, IL-12, IL-13, and tumor necrosis factor- α (TNF- α ), was more evident than that of others. The extent of arteritis correlated with the plasma TNF- α levels, suggesting a pivotal role of TNF- α in KD. In conclusion, etanercept was most effective in suppressing CAWS-induced vasculitis and can be a new therapeutic intervention for KD.
    International journal of vascular medicine 03/2013; 2013:543141. DOI:10.1155/2013/543141
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