Defining Risk Factors for Red Man Syndrome in Children and Adults

Background: Red man syndrome (RMS) is a well-known adverse reaction that occurs in pediatric patients receiving vancomycin, yet reported prevalence is varied, and characteristics and risk factors are not well understood. Our objective was to determine the prevalence, characteristics and risk factors for RMS in pediatric patients receiving vancomycin, including contributing genetic factors. Methods: A multicenter retrospective study of 546 subjects (0.5-21 years) who received at least 1 dose of intravenous vancomycin was conducted. Demographic and symptom data were collected through chart review and parent/nurse report. Genotype analysis included 10 single nucleotide polymorphisms in the histamine pathway. Results: RMS was observed in 77 (14%) subjects receiving vancomycin. Forty percent of subjects with RMS symptoms developed rash, pruritis and flushing, without hypotension. Antecedent antihistamine use was identified as a risk factor for RMS (P < 0.001). Multivariate regression analysis identified age > 2 years (P = 0.008), previous RMS (P < 0.001), vancomycin dose (P = 0.02) and vancomycin concentration (P = 0.017) as RMS risk factors, whereas African American race was protective (P = 0.011). We observed an apparent association between RMS and a single nucleotide polymorphism in the diamine oxidase gene (P = 0.044); however, no associations were revealed by multifactor dimensionality reduction analysis. Conclusions: RMS is a common adverse event in children receiving vancomycin. Identified risk factors are Caucasian ethnicity, age. >= 2 years, previous RMS history, vancomycin dose. >= 10 mg/kg, vancomycin concentration. >= 5 mg/mL and antecedent antihistamine use. Known genetic variants in histamine metabolism or receptors do not appear to be substantial contributors to risk of RMS.