Infliximab for intravenous immunoglobulin-resistant Kawasaki disease complicated with cholestatic hepatitis: a case report and discussion on coronary artery aneurysm prevention

英夫利昔单抗治疗静脉注射免疫球蛋白耐药性川崎病合并胆汁淤积性肝炎:病例报告及冠状动脉瘤预防探讨

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Abstract

BACKGROUND: Kawasaki disease (KD) is the leading cause of acquired heart disease in children under 5 years of age worldwide. Approximately 15%-20% of KD patients are resistant to intravenous immunoglobulin (IVIG), and these patients have a significantly higher risk of developing coronary artery aneurysms (CAAs), a severe complication leading to long-term cardiovascular morbidity. Cholestatic hepatitis is a rare manifestation of KD, which further increases the difficulty of clinical treatment. This study reports a case of IVIG-resistant KD complicated with cholestatic hepatitis treated with infliximab, and explores the clinical challenges in preventing CAA progression. CASE REPORT: A 2-year-old Han Chinese male presented with persistent fever as the initial symptom, followed by typical clinical manifestations of KD and cholestatic hepatitis. Initial treatment with high-dose IVIG (2 g/kg) combined with clopidogrel (1 mg/kg/day) was ineffective. A second dose of IVIG (1 g/kg) combined with high-dose methylprednisolone pulse therapy also failed to control the disease. On the ninth day of illness, salvage therapy with the tumor necrosis factor-alpha (TNF-α) inhibitor infliximab (5 mg/kg) was administered, and the child's fever subsided rapidly within 24 h. Subsequent laboratory examinations showed that inflammatory indicators [C-reactive protein (CRP), erythrocyte sedimentation rate (ESR)] and liver function indicators [alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, total bile acids (TBA)] improved significantly. However, despite effective inflammation control, echocardiographic follow-up revealed progressive development of CAAs, eventually forming giant CAAs. CONCLUSION: Infliximab can effectively suppress systemic inflammation and improve liver function in patients with IVIG-resistant KD complicated with cholestatic hepatitis. However, the development of giant CAAs in this case underscores the dissociation between systemic inflammation control and coronary protection, highlighting the critical importance of optimizing the timing of infliximab administration. Further randomized controlled trials are needed to clarify the optimal timing, dose, and patient selection criteria for infliximab in the treatment of IVIG-resistant KD.

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