title: The Pholcodine Case. Cough Medicines, IgE-Sensitization, and Anaphylaxis:  A Devious Connection.
abstract: : The Scandinavian data on pholcodine (PHO) strongly indicates that there is a biological chain from PHO exposure through IgE-sensitization to IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBA). PHO is probably one of the strongest inducer of an IgE antibody response known. Of individuals taking PHO in cough medicines, over-the-counter accessibility to large populations, as many as 20 to 25% may become IgE sensitized. Once sensitized, PHO re-exposure will booster IgE antibody levels and IgE by around 100-fold. PHO is monovalent for 2 non-cross-reacting epitopes the quaternary ammonium ion (QAI), the main allergenic epitope of NMBA, and a non-QAI epitope. Thus, PHO most unlikely would initiate an allergic inflammatory response. Consequently, IgE sensitization is not revealed by obvious clinical signs, neither through tests based on IgE-sensitized effector cells. Therefore, it will escape detection if not assayed serologically. However, when subjected to general anesthesia, and thus the IgE-sensitized individual is administered a bivalent NMBA intravenously, the unrecognized presence of serum IgE antibodies to QAI may increase the risk of anaphylaxis 200- to 300-fold. Severe damages to patient's health can result, and mortality rates of 3 to 10% are reported. The Scandinavian experience indicates that the chain of events can efficiently be avoided by stopping PHO exposure: Within 1 year, the prevalence of IgE sensitization to PHO and QAI decreases significantly, and after 2 to 3 years, the numbers of reported anaphylactic reactions decreases equally so.
authors.affiliation: 1Laboratory of Clinical Biochemistry and Section for Clinical Allergology, Department of Occupational Medicine, Haukeland University Hospital, Bergen, Norway 2Institute of Medicine, University of Bergen, Norway 3Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden 4Department of Clinical Immunology and Transfusion Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Florvaag
authors.forename: S G O
authors.initials: SG
authors.lastname: Johansson