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 oxidasegene (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.
Department of Pediatrics, Medical Research, Children's Mercy Hospitals and Clinics and the University of Missouri-Kansas City, Kansas City, MO 64108, USA. amyers@cmh.edu
Angela L
AL
Myers
Andrea
A
Gaedigk
Hongying
H
Dai
Laura P
LP
James
Bridgette L
BL
Jones
Kathleen A
KA
Neville
D000293:Adolescent; D006631:Amine Oxidase (Copper-Containing) / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D004890:Erythema / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D005076:Exanthema / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D005260:Female; D005483:Flushing / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D006632:Histamine / Q000378:metabolism; D006760:Hospitalization; D006801:Humans; D007223:Infant; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011537:Pruritus / Q000139:chemically induced* / Q000188:drug therapy / Q000235:genetics; D012307:Risk Factors; D013577:Syndrome; D014640:Vancomycin / Q000008:administration & dosage / Q000009:adverse effects*; D055815:Young Adult
D014640:Vancomycin; D006632:Histamine; D006631:Amine Oxidase (Copper-Containing)