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Objective: To assess the clinical utility and safety of a strategy for refractory Kawasaki disease, defined by Egami score ≥3., Study Design: First-line treatment was with intravenous methylprednisolone (30 mg/kg, 2 hours, 1 dose) plus intravenous immunoglobulin (2 g/kg, 24 hours) treatment. Patients resistant to first-line treatment received additional intravenous immunoglobulin as a second-line treatment. Patients resistant to second-line treatment who had received Bacillus Calmette-Guérin vaccination 6 months earlier were treated with infliximab; otherwise, plasma exchange was performed. A total of 71 refractory patients with Kawasaki disease (median age: 2.4 years) of 365 patients with Kawasaki disease were treated according to our strategy from April 2007 to April 2016. Treatment resistance was defined as a persistent fever at 36 hours after treatment. We evaluated coronary artery lesions at the time of the diagnosis, at 1 month, and at 1 year after the diagnosis in accordance with the American Heart Association guidelines and the criteria of the Japanese Ministry of Health, Labour, and Welfare., Results: First-line therapy was effective for 58 of 71 patients (81.6%), and second-line therapy was effective for 9 of 13 patients (69.2%). At third line, 3 patients were treated by infliximab, and 1 was treated with plasma exchange. Of the 18 patients with coronary artery abnormalities at diagnosis, 13 patients at 1 month and 6 patients at 1 year had coronary artery dilatation (median z score 3.0, 2.6, and 1.4, respectively). There were no patients with coronary artery aneurysm (CAA)., Conclusions: Our strategy for refractory Kawasaki disease was safe and effective in preventing CAA., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Infliximab (IFX), a known monoclonal antibody against tumor necrosis factor-α (TNF-α), is used to treat Kawasaki disease (KD) patients with intravenous immunoglobulin (IVIG) resistance. The transcriptional modulation of inflammation following IFX therapy has not been reported in KD patients., Methods: We investigated the transcript abundance profiles in whole blood obtained from eight IVIG-resistant KD subjects treated with IFX therapy using microarray platforms and compared them with those in initially IVIG-responsive subjects. A pathway analysis was performed using WikiPathways to search for the biological pathways of the transcript profiles. Four transcripts changed by IFX therapy were subsequently validated using quantitative real-time polymerase chain reaction., Results: The pathway analysis showed the reduced abundance of transcripts in the nucleotide-binding oligomerization domain, matrix metalloproteinase (MMP), and inflammatory cytokine pathways and the increased abundance of transcripts in the T-cell receptor, apoptosis, TGF-β, and interleukin-2 pathways. Additionally, the levels of four transcripts (peptidase inhibitor-3, MMP-8, chemokine receptor-2, and pentraxin-3) related to KD vasculitis and IVIG resistance decreased after IFX therapy., Conclusion: The administration of IFX was associated with both the signaling pathways of KD inflammation and several transcripts related to IVIG resistance factors. These findings provide strong theoretical support for the use of IFX in KD patients with IVIG resistance.

Objective: This study examined the clinical efficacy and safety of intravenous methylprednisolone-pulse plus intravenous immunoglobulin (IVIG) combination therapy (IVMP+IVIG) for the initial treatment of patients predicted to have refractory Kawasaki disease (KD)., Methods: One hundred twenty-two patients with KD were studied at Kitasato University. Refractory KD was predicted at diagnosis using the Egami score, and the patients were randomly divided to receive either IVMP+IVIG or IVIG alone. The Egami score is used to predict refractory KD patients before treatment using the patient's age, days of illness, platelet count, C-reactive protein, and alanine aminotransferase level (cutoff: ≥3 points; 78% sensitivity and 76% specificity)., Results: Forty-eight patients (39.3%) were predicted to have refractory KD on the basis of the Egami score. The predicted IVIG responders (n = 74) received the standard therapy. The 48 predicted refractory KD patients were randomly assigned to a single-IVIG group (n = 26) or an IVMP+IVIG group (n = 22). Nineteen of the 22 patients (86.4%) in the IVMP+IVIG group had a prompt defervescence compared with 6 of the 26 patients (23.1%) in the single-IVIG group. The number of patients who had a z score ≥2.5 at 1 month was significantly higher in the single-IVIG group than in the IVMP+IVIG group. No serious adverse events were observed in either treatment group., Conclusion: This study demonstrated that IVMP+IVIG therapy is safe and effective for KD patients predicted as refractory.

Background: We compared the clinical utility of additional intravenous immune globulin (IVIG) therapy with the clinical utility of steroid pulse therapy in patients with IVIG-resistant Kawasaki disease., Methods: We enrolled 164 patients with Kawasaki disease who were treated with a single dose of IVIG (2 g/kg) and aspirin (30 mg/kg per day). Twenty-seven of these patients (16%) were resistant to the initial IVIG treatment. We compared the effectiveness of treatment strategies for the initial IVIG-resistant 27 patients, 14 of these patients were treated with additional IVIG therapy, and the other 13 patients were treated with steroid pulse therapy (methylprednisolone 30 mg/kg per day for 3 days)., Results: Three patients in the group receiving additional IVIG treatment had coronary artery aneurysms (21.4%), no patients had coronary artery aneurysm in the steroid pulse therapy group; the difference in the incidence of coronary artery aneurysm was not statistically significant. The duration of high fever after additional treatment in the steroid pulse therapy group (1 ± 1.3 days) was significantly shorter than that in the additional IVIG treatment group (3 ± 2.4 days; P < 0.05). The medical costs were significantly lower in the steroid pulse therapy group than in the additional IVIG treatment group., Conclusion: Steroid pulse therapy was useful to reduce the fever duration and medical costs for patients with Kawasaki disease. Steroid pulse therapy and additional IVIG treatment were not significantly different in terms of preventing the development of coronary artery aneurysm.