title: Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin.
abstract: BACKGROUND
  Kawasaki disease (KD) is a systemic vasculitis of childhood involving coronary arteries. Treatment for intractable cases at a higher risk of cardiac sequelae remains controversial.
  
  
  METHODS
  Clinical outcomes of KD patients diagnosed in Yamaguchi prefecture, Japan between 2003 and 2014 were analyzed using the medical records from all 14 hospitals covering the prefecture. The study included 1487 patients (male:female, 873:614; median age at diagnosis, 24months).
  
  
  RESULTS
  The proportion of initial intravenous immunoglobulin (IVIG)-resistant patients increased from 7% to 23% during this decade, although no patients died. Twenty-four patients developed coronary artery lesions (CALs) over one month after the KD onset. The incidence of CAL in patients who received corticosteroid during the disease course (10/37; 27.0%) was higher than that in those who did not (14/1450; 0.97%, p=2.0×10(-35)). Nine patients who responded to initial IVIG plus corticosteroids had no CAL. Conversely, IVIG-resistant patients with alternate corticosteroid therapy more frequently developed CAL than those without it (10/28; 35.7% vs. 5/194; 2.6%, p=8.9×10(-10)). Multivariate analyses indicated corticosteroid therapy (p<0.0001), hyperbilirubinemia (p=0.0010), and a longer number of days before treatment (p=0.0005) as risk factors associated with CAL over a month after onset. The odds ratio of corticosteroid use increased from 18.3 to 43.5 if the cases were limited to initial IVIG non-responders and corticosteroid free-IVIG responders.
  
  
  CONCLUSIONS
  IVIG-failure has recently increased. The incidence of CAL increased in intractable cases with prolonged corticosteroid use. Corticosteroid may not be alternate choice for IVIG-failure to reduce the risk of cardiac sequelae.
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Kibata
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan. Electronic address: shunji@yamaguchi-u.ac.jp.
authors.forename: Shunji
authors.initials: S
authors.lastname: Hasegawa
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsushige
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kusuda
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Hoshide
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Seigo
authors.initials: S
authors.lastname: Okada
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Wakiguchi
authors.affiliation: Division of Pediatrics, National Hospital Organization Iwakuni Clinical Center, Iwakuni, Japan.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Moriwake
authors.affiliation: Division of Pediatrics, JCHO Tokuyama Central Hospital, Shunan, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Uchida
authors.affiliation: Division of Pediatrics, Yamaguchi Red Cross Hospital, Yamaguchi, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Ohbuchi
authors.affiliation: Division of Pediatrics, Yamaguchi-ken Saiseikai Shimonoseki General Hospital, Shimonoseki, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwai
authors.affiliation: Division of Pediatrics, Yamaguchi Grand Medical Center, Hofu, Japan.
authors.forename: Masanari
authors.initials: M
authors.lastname: Hasegawa
authors.affiliation: Department of Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ichihara
authors.affiliation: Department of Public Health, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yashiro
authors.affiliation: Department of Public Health, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Makino
authors.affiliation: Department of Public Health, Jichi Medical University, Shimotsuke, Japan.
authors.forename: Yosikazu
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Ube, Japan.
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000008:administration & dosage*; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D007564:Japan / Q000453:epidemiology; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies
chemical_list: D016756:Immunoglobulins, Intravenous
keywords: Coronary artery lesion; Corticosteroid; Intravenous immunoglobulin