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Genetic Polymorphisms Associated With Histamine Disposition in Children With Vancomycin Associated Red Man Syndrome (RMS)

Phase 4
6 Months
21 Years
Not Enrolling
Red Man Syndrome

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Trial Information

Genetic Polymorphisms Associated With Histamine Disposition in Children With Vancomycin Associated Red Man Syndrome (RMS)

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.

Inclusion Criteria:

- Patients must have received vancomycin

Exclusion Criteria:

- Patients who have received antihistamines at the time of vancomycin administration or

- Patients who have been on steroids or tricyclic antidepressants within 30 days prior
to the vancomycin administration

- People receiving ECMO or have multiorgan failure

- Currently receiving dialysis

Type of Study:


Study Design:

Observational Model: Case Control, Time Perspective: Prospective

Outcome Measure:

Presence or abscence of genetic polymorphisms in the histamine pathway in patients with vancomycin related RMS.

Outcome Time Frame:

During Hospital Admission

Safety Issue:


Principal Investigator

Angela Myers, MD, MPH

Investigator Role:

Principal Investigator

Investigator Affiliation:

Children's Mercy Hosptials and Clinics


United States: Federal Government

Study ID:




Start Date:

January 2008

Completion Date:

October 2011

Related Keywords:

  • Red Man Syndrome
  • Multiple Endocrine Neoplasia



Children's Mercy Hospital & ClinicsKansas City, Missouri  64108