title: Variability in Response to Intravenous Immunoglobulin in the Treatment of Kawasaki Disease.
abstract: To characterize the pattern of temperature response to intravenous immunoglobulin (IVIG) infusion in patients with Kawasaki disease (KD).
  
  
  
  Patients nonresponsive to IVIG (axillary temperature ≥37.5°C >24 hours after end of IVIG) were identified. Each patient with IVIG-nonresponsive KD was matched to a control patient with IVIG-responsive KD of the same age, sex, and duration of fever before IVIG. Hourly temperature profiles were obtained from immediately before the start of IVIG infusion until complete defervescence.
  
  
  
  A total of 182 patients nonresponsive to IVIG were matched (total n = 364). Nonresponders were further classified as partial nonresponders (68%) (axillary temperature decreased to <37.5°C but fever recurred) and complete nonresponders (32%) (axillary temperature consistently ≥37.5°C throughout IVIG treatment). The temperature profile during IVIG infusion was similar between responders and partial nonresponders (EST: -0.061 [0.007]°C/h, P < .001 for responders vs EST: -0.027 (0.012)°C/h, P = .03 for partial nonresponders [responders vs partial nonresponders, P = .65]), where EST is the parameter estimate from the regression model, representing the change in degrees Celsius for each hour since start of IVIG. In complete nonresponders, IVIG was not associated with significant decreases in temperature (EST: -0.008 [0.010]°C, P = .42). Factors associated with complete (vs partial) nonresponse included laboratory-confirmed infection, greater C-reactive protein, and IVIG brand. Defervescence in partial nonresponders was achieved with a second IVIG dose for 72% of patients compared with 58% of complete nonresponders (P = .001). Complete nonresponders were more likely to develop coronary artery aneurysms vs partial nonresponders (OR: 2.4 [1.1-5.4], P = .03) or responders (OR: 3.2 [1.5-6.9], P = .002).
  
  
  
  Nonresponse to initial IVIG can be further characterized by temperature profile, and complete nonresponders may require more aggressive second-line therapy.
authors.affiliation: Labatt Family Heart Centre, University of Toronto, The Hospital for Sick Children, Toronto, Canada. Electronic address: mallory.downie@sickkids.ca.
authors.forename: Mallory L
authors.initials: ML
authors.lastname: Downie
authors.affiliation: Labatt Family Heart Centre, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.affiliation: Division of Rheumatology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Giuseppe A
authors.initials: GA
authors.lastname: Latino
authors.affiliation: Labatt Family Heart Centre, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Tanveer H
authors.initials: TH
authors.lastname: Collins
authors.affiliation: Labatt Family Heart Centre, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Nita
authors.initials: N
authors.lastname: Chahal
authors.affiliation: Division of Rheumatology, Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Rae S M
authors.initials: RS
authors.lastname: Yeung
authors.affiliation: Labatt Family Heart Centre, University of Toronto, The Hospital for Sick Children, Toronto, Canada.
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
mesh_terms: D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D009080:Mucocutaneous Lymph Node Syndrome / Q000150:complications / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous
keywords: inflammatory heart disease; pediatrics; resistance; risk factors