Chlorhexidine is a cationic chlorophenyl biguanido antiseptic and disinfectant and is commonly used as the diacetate or digluconate salt. Its structure is symmetrical with two identical epitopes, which implies that chlorhexidine per se would be capable of cross linking IgE antibodies on the surface of mast cells and basophiles thereby eliciting allergic reactions by histamine release in sensitized individuals. This mechanism has been demonstrated with similar divalent drugs such as the muscle relaxant suxamethonium (1).
Exposure to the allergen often occurs as skin disinfection prior to surgery and blood tests or by urinary catheterization, disinfection of a drain insertion site, or placement of a central venous catheter. Exposure also occurs upon use of gel in vaginal and rectal examinations and in connection with dental procedures. Chlorhexidine exposure is also wide-spread in homes from use of numerous products such as cleaning fluids, toothpastes, mouth rinses etc.
No reports on cross-reactivity have been published.
Delayed cutaneous reactions such as contact dermatitis are well known and have been reported since the 1960s (2). Immediate reactions, including anaphylactic shock, have been reported since 1984 (3) but are considered to be rare; indeed, during a ten-year period only 50 case reports of chlorhexidine-related anaphylaxis were published worldwide (4). However, the true incidence of anaphylaxis to chlorhexidine is not known and it is likely to be underestimated. This may be due to the fact that chlorhexidine is not a drug, but a disinfectant agent, and is thus rarely suspected in connection with anaphylaxis.
Anaphylactic reactions to chlorhexidine have been shown to be IgE mediated in a number of studies. In 1986 Ohtoshi et al. detected chlorhexidine-specific IgE antibodies in sera from eight patients who suffered from anaphylactic shock (5). In the following years Layton (6) and Baldo (7) demonstrated IgE antibodies against chlorhexidine in sera of a small number of patients. More recently, ImmunoCAP Allergen c8 Chlorhexidine has been evaluated at the Danish Anaesthesia Allergy Centre (DAAC), and in this study 11 of 12 patients with anaphylaxis in connection with anaesthesia and positive skin tests to chlorhexidine were found to have IgE antibodies to chlorhexidine. A control group of 10 patients, who all had a negative skin test to chlorhexidine, did not have IgE to chlorhexidine (8). In a recent Belgian study four allergic reactions during perioperative skin disinfection and urethral catheterization were reported. IgE antibodies were detected in all four of these patients using ImmunoCAP Allergen c8 Chlorhexidine, demonstrating a good correlation with skin tests and the basophile stimulation test (BAT) (9).
Allergy to chlorhexidine has some features that deserve attention. Chlorhexidine allergy often presents with mild cutaneous symptoms, but has the potential to cause life-threatening anaphylaxis at a later occasion. Reactions typically occur 20-40 minutes after initial exposure. As chlorhexidine is not a drug, but a disinfectant agent, it can be overlooked as the cause of anaphylaxis during anaesthesia. Obviously, this leads to the risk of potentially dangerous re-exposure.
Compiled by Dr Lennart Venemalm, Phadia
- Didier, A., Cador, D., Bongrand, P., Furstoss, R., Fourneron, P., Senft, M., Philip Joet, F., Charpin, D., Charpin, J., Vervloet, D. Role of the quaternary ammonium ion determinants in allergy to muscle relaxants. J Allergy & Clin Immunol 1987; 79(4): 578-84.
- Birdwood, B. Reaction to Chlorhexidine and Cetrimide. Lancet 1965 Mar 20; 43: 651-52.
- Nishioka, K., Doi, T., Katayama, I. Histamine release in contact urticaria. Contact Dermatitis 1984; 11: 191.
- Beaudouin, E., Kanny, G., Morisset, M., Renaudin, J.M., Mertes, M., Laxenaire, M.C., Mouton, C., Jacson, F., Moneret-Vautrin, D.A. Immediate hypersensitivity to chlorhexidine: literature review. Allerg Immunol 2004; 36 (4): 123-26.
- Ohtoshi, T., Yamauchi, N., Tadokoro, K., Miyachi, S., Suzuki, S., Miyamoto, T., Muranaka, M. IgE antibody-mediated shock reaction caused by topical application of chlorhexidine. Clin Allergy 1986; 16 (2): 155-61.
- Layton, G.T., Stanworth, D.R., Amos, H.E. The incidence of IgE and IgG antibodies to chlorhexidine. Clin Exp Allergy 1989; 19(3): 307-14.
- Pham, N.H., Weiner, J.M., Reisner, G.S., Baldo, B.A. Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin E antibodies and identification of an allergenic determinant. Clin Exp Allergy 2000; 30(7): 1001-07.
- Garvey, L., Kroigaard, M., Poulsen, L., Skov, P., Mosbech, H., Malling, H., Venemalm, L., Degerbeck, F., Husum, B. IgE-mediated allergy to chlorhexidine in twelve skin test positive patients – diagnosis verified by specific IgE measurement and histamine release. Data presented at the XXV Congress of the European Academy of Allergology and Clinical Immunology, June 2006.
- Ebo, D.G., Bridts, C.H., Stevens, W.J. IgE-mediated anaphylaxis from chlorhexidine: diagnostic possibilities. Contact Dermatitis 2006; 55(5): 301-02.