Seasonality of i.v. immunoglobulin responsiveness in Kawasaki disease

Pediatr Int. 2019 Jun;61(6):539-543. doi: 10.1111/ped.13863. Epub 2019 Jun 18.

Abstract

Background: Evidence suggests that seasonal variation in the onset of Kawasaki disease (KD) exists worldwide. Whether a seasonal component to successful i.v. immunoglobulin (IVIG) therapy exists in KD-positive children, however, is unknown. We addressed this question by focusing on patients with primary onset KD who were non-responsive to IVIG treatment, in the large nationwide Japanese KD survey datasets from 2009 to 2016.

Methods: In these datasets, the IVIG therapy non-responders were defined as patients whose fever persisted ≥24 h or recurred ≤24 h after the end of the initial IVIG treatment (dosage, 2,000 mg/kg). Those who successfully responded to this treatment were defined as IVIG responders. The consecutive monthly trend of the proportion of IVIG non-responders was analyzed throughout the study period to investigate seasonal periodicity on Fourier analysis, and the monthly distributions of non-responders and responders were compared.

Results: From a total of 113 691 KD-positive patients, 15.7% were IVIG non-responders, and 61% were male. The proportion of non-responders increased across each calendar year with fluctuation, and Fourier analysis indicated seasonal periodicity. The seasonality effect differed between responders and non-responders, with the proportion of responders tending to increase in autumn through winter, while the non-responders showed a decreasing trend in autumn. The seasonality effect tended to differ by sex.

Conclusions: The results indicate that the currently unknown etiological agents of KD might differ between IVIG responders and non-responders. In addition, immune reactivity against such agents possibly differs by sex in the IVIG non-responders.

Keywords: Kawasaki disease; epidemiology; i.v. immunoglobulin; infectious disease; seasonal variation.

MeSH terms

  • Child
  • Child, Preschool
  • Female
  • Health Surveys
  • Humans
  • Immunoglobulins, Intravenous / therapeutic use*
  • Immunologic Factors / therapeutic use*
  • Infant
  • Infant, Newborn
  • Japan
  • Male
  • Mucocutaneous Lymph Node Syndrome / drug therapy*
  • Mucocutaneous Lymph Node Syndrome / etiology
  • Retrospective Studies
  • Seasons*
  • Treatment Outcome

Substances

  • Immunoglobulins, Intravenous
  • Immunologic Factors