Red Man Syndrome Clinical Trial
Official title:
Genetic Polymorphisms Associated With Histamine Disposition in Children With Vancomycin Associated Red Man Syndrome (RMS)
This study proposes to identify patients who developed RMS with vancomycin infusion, and
determine presence or absence of variant alleles involved in histamine biotransformation.
The implications of this study are important, as identification of variant alleles in these
patients, may alter the current standard of care for vancomycin infusions.
The hypothesis of this study is that the development of red man syndrome (RMS) during
receipt of intravenous vancomycin is associated with the presence of variant alleles for
genes involved in the histamine pathway. The primary outcome that will be measured will be
the history of RMS and the presence or absence of variant alleles for the genes responsible
for histamine metabolism (i.e. histamine n-methyltransferase and diamine oxidase). As a
secondary endpoint, the study will also attempt to determine the incidence of RMS in
pediatric patients.
Vancomycin has been utilized as an antimicrobial therapeutic agent for serious gram positive
infections for more than half a century.The pharmacokinetics of vancomycin has been well
studied, and in general there are few side effects from this medication. The most common
side effect that occurs with receipt of vancomycin is red man syndrome (RMS), which is also
known as red neck, or red person syndrome.1 RMS encompasses a spectrum that ranges from a
mild reaction such as flushing, urticarial rash, pruritis, to a severe reaction that
includes generalized erythema,intense pruritis, and even hypotension. RMS has been estimated
to occur in 5- 50% of hospitalized patients who receive this drug.
RMS is considered an anaphylactoid type of reaction that is due to mast cell degranulation
with a concomitant rise in blood histamine levels. The resultant symptomatology varies from
mild itching and erythematous rash to a more generalized reaction with hypotension. This
reaction has been shown to be modified by pre-treatment with various types of antihistamines
including diphenhydramine and cimetidine.
There is now evidence to suggest that altered histamine metabolism contributes to the
pathogenesis of various disorders. Histamine is almost exclusively metabolized by the
enzymes histamine N-methyltranserase (HNMT)and diamine oxidase (DAO) both of which are
polymorphically expressed in people with varying frequencies.HNMT catalyzes the N-
methylation of histamine. This is the predominant pathway for histamine
metabolism,accounting for 50-80% of its biotransformation. Diamine oxidase (DAO) likely
contributes in a significant manner of the remaining metabolism of histamine as only 2-3% of
this autocoid is excreted unchanged in the urine. It is plausible that allelic variants of
HNMT and/or DAO may contribute to histmaminergic reactions in a given patient with resultant
propagation of its pharmacologic effects, and that polymorphically expressed enzymes
primarily responsible for terminating the pharmacologic activity of histamine (via
biotransformation)may play a crucial role in determining disease phenotype for disorders
(e.g., RMS) where histamine is a key mediator.
This is a prospective study that will be conducted over a one year period of time. Eligible
patients will be identified by a search of patients who are receiving vancomycin therapy
throughout the study period. Chart review/patient interview will then be performed to
identify patients who developed symptomatology consistent with RMS while receiving
vancomycin infusion. For the purposes of this study, red man syndrome (RMS) will be defined
as: erythematous rash, flushing of the face, neck, or torso, itching, or a lowering of
systolic or diastolic blood pressure by >10mm/hg. A subset of patients who remained
asymptomatic throughout their vancomycin therapy will also be evaluated as a control group.
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Observational Model: Case Control, Time Perspective: Prospective