Clinical Trial: Vancomycin Associated Red Man Syndrome (RMS)
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: Genetic Polymorphisms Associated With Histamine Disposition in Children With Vancomycin Associated Red Man Syndrome (RMS)
Brief Summary:
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.
Detailed Summary:
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
Sponsor: Children's Mercy Hospital Kansas City
Current Primary Outcome: Presence or abscence of genetic polymorphisms in the histamine pathway in patients with vancomycin related RMS. [ Time Frame: During Hospital Admission ]
Original Primary Outcome: Presence or abscence of genetic polymorphisms in the histamine pathway in patients with vancomycin related RMS.
Current Secondary Outcome:
Original Secondary Outcome:
Information By: Children's Mercy Hospital Kansas City
Dates:
Date Received: January 14, 2009
Date Started: January 2008
Date Completion:
Last Updated: October 11, 2011
Last Verified: October 2011
