Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin Eantibodies and identification of an allergenic determinant

Background There are many reports of allergic reactions, including anaphyla xis, following exposure to chlorhexidine. Reactions may occur via contact w ith the skin and mucous membranes or from catheters treated with the antiba cterial 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 sensit ive subjects. Objectives 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 anaphylacti c patient. Results were analysed to define the complete drug allergenic det erminant 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 th e terminal groups at each end of the chlorhexidine molecule, alone, did not account for antibody recognition of the antibacterial agent. Although chlo rguanide and alexidine, the structures of which each comprise part of the c hlorhexidine 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 symmetrica l 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 con clusion that the whole chlorhexidine molecule is complementary to the IgE a ntibody combining sites and that the 4-chlorophenol, biguanide and hexameth ylene structures together comprise the allergenic determinant. Hence, like one of the trimethoprim determinants identified, but unlike most drug aller genic determinants identified so far, the chlorhexidine allergenic determin ant identified here encompasses the entire molecule.