Vancomycin Associated Red Man Syndrome (RMS)
Condition: Red Man Syndrome
MeSH terms: Multiple Endocrine Neoplasia; Syndrome
Study type: Observational

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 description: 
      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.
    

Observational model: Case-Control
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        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.
      
Biospecimen description: 
      Frozen blood has been maintained for future genetic studies