title: Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin E antibodies and identification of an allergenic determinant.
abstract: BACKGROUND
  There are many reports of allergic reactions, including anaphylaxis, following exposure to chlorhexidine. Reactions may occur via contact with the skin and mucous membranes or from catheters treated with the antibacterial agent. Apart from implicating chlorguanide in immunoglobulin (Ig) E antibody-binding studies on serum from an anaphylactic patient, little work has been done on the molecular basis of recognition of the agent in sensitive subjects.
  
  
  OBJECTIVE
  The molecular basis of IgE-binding to chlorhexidine was closely examined with the view of defining its fine structural recognition features by antibodies from a subject who experienced anaphylaxis following contact with the antiseptic.
  
  
  METHODS
  Tryptase determinations, different drug-solid phases, immunoassays and quantitative hapten inhibition studies with chlorhexidine and selected structural analogues were employed together with serum from the anaphylactic patient. Results were analysed to define the complete drug allergenic determinant and to identify the important structural features complementary to the IgE antibody combining sites.
  
  
  RESULTS
  The subject's serum tryptase levels sampled after the reaction were elevated and employment of a chlorhexidine-EA Sepharose solid phase showed the presence of serum IgE antibodies to the drug. Lack of inhibition by 4-chlorophenol and other selected substituted phenyl compounds showed that the terminal groups at each end of the chlorhexidine molecule, alone, did not account for antibody recognition of the antibacterial agent. Although chlorguanide and alexidine, the structures of which each comprise part of the chlorhexidine molecule, showed significant inhibition of the binding of IgE antibodies to chlorhexidine, neither compound was as potent an inhibitor as chlorhexidine itself. Two molecules of chlorguanide make up the symmetrical molecule of chlorhexidine while the interior structure of alexidine (that is excluding the terminal 2-ethylhexyl groups) is identical to part of the chlorhexidine molecule.
  
  
  CONCLUSIONS
  Taken together, for this patient, these results lead to the conclusion that the whole chlorhexidine molecule is complementary to the IgE antibody combining sites and that the 4-chlorophenol, biguanide and hexamethylene structures together comprise the allergenic determinant. Hence, like one of the trimethoprim determinants identified, but unlike most drug allergenic determinants identified so far, the chlorhexidine allergenic determinant identified here encompasses the entire molecule.
authors.affiliation: Molecular Immunology Unit, Kolling Institute of Medical Research, Royal North Shore Hospital of Sydney, St Leonards, NSW 2065, Australia.
authors.forename: N H
authors.initials: NH
authors.lastname: Pham
authors.forename: J M
authors.initials: JM
authors.lastname: Weiner
authors.forename: G S
authors.initials: GS
authors.lastname: Reisner
authors.forename: B A
authors.initials: BA
authors.lastname: Baldo
mesh_terms: D000368:Aged; D000485:Allergens / Q000009:adverse effects* / Q000276:immunology; D000707:Anaphylaxis / Q000139:chemically induced* / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001645:Biguanides / Q000276:immunology; D001666:Binding Sites, Antibody / Q000276:immunology; D002710:Chlorhexidine / Q000009:adverse effects* / Q000276:immunology; D002733:Chlorophenols / Q000276:immunology; D004202:Disinfectants / Q000009:adverse effects* / Q000276:immunology; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000276:immunology; D000939:Epitopes / Q000276:immunology*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008297:Male
chemical_list: D000485:Allergens; D001645:Biguanides; D002733:Chlorophenols; D004202:Disinfectants; D000939:Epitopes; D007073:Immunoglobulin E; C029107:4-chlorophenol; D002710:Chlorhexidine