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Chlorhexidine anaphylaxis in Auckland.
- Anne Wills (5 February 2009)
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Allergy to preservatives
- Craig A Patterson (11 December 2008)
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Anne Wills, Specialist Anaesthetist
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Nigel Harper and his associates' case presentations and thorough discussion relating to chlorhexidine anaphylaxis, BJA,2009:102(1)69-75 prompted me to review our experience of chlorhexidine anaphylaxis at the Anaesthetic Allergy Testing Clinic within the Auckland City Hospital. This Clinic provides an anaesthetic allergy testing service for the Greater Auckland region of New Zealand. Some referrals from smaller centres in the country are also received. Since 1998, we have encountered twenty-six patients with a clinical picture in-keeping with anaphylaxis to chlorhexidine. Most of these patients had raised mast-cell tryptase levels and all tested positive on skin-prick testing, using 2% aqueous skin-wash. In every case (except one), we performed skin-tests against all agents administered prior to the adverse event. These include anaesthetic agents, antibiotics and ancillary drugs such as latex and chlorhexidine. Harper et al noted responses to Instillagel(R) which contains 0.25% chlorhexidine in 2% lignocaine gel. The urinary lubricant used in Auckland is Urosyringe(R)(AstraZenica). This contains 0.05% chlorhexidine in 2% lignocaine gel. Our first patient, a woman, in 1998, responded adversely to the skin-wash Hibitane(R)(1% chlorhexidine in 70% alcohol). However, the majority of cases were in response to the urinary lubricant. Most were men, and three occurred in the recovery room when awake. Three patients has anaphylaxis to chlorhexidine immediately following the insertion of chlorhexidine-impregnated central lines. It is of interest that chlorhexidine products are increaseingly being recommended for dental hygiene, periodontal care and implant surgery. Savacol(R)(Colgate) is frequently used by dental surgeons. The concentrated solution contains 2mg/ml, but when appropriately diluted, it becomes a 0.2% solution of chlorhexidine as the dental wash. We receive many referrals each year from dental surgeons and general practitioners requesting testing for the local anaesthetic agents, on the grounds of the patients' histories, although all are aware that allergy to the now commonly-used amide-amide local anaesthetics is extremely rare. Adverse reactions are usually due to vaso-vagal responses, hyperventilation or inadvertent intravascular injection. Nevertheless, latex testing has been included in testing these patients. Now, based on our perception that chlorhexidine is a significant cause of Type 1 hypersensitivity reactions, we are including the skin-prick test for this agent in the protocol for assessment of these patients. Another issue raised by the authors was the fact that the serum mast- cell tryptase(MCT) is not always raised in an anaphylactic reaction. As mentioned, this is probably due to an immediate basophylic response. Basophils are circulating blood cells that contain virtually no tryptase; in contrast, tryptase-rich mast-cells are present mainly in connective tissue and also in mucosae. We too have noted an increase in referrals of subjects with possible anaphylactic reactions in the absence of a MCT rise. There is an increasing awareness of amongst Auckland anaesthetists of peri-operative anaphylaxis, so it is postulated that the adverse clinical events are diagnosed and treated early, prior to the cascade of anaphylaxis reaching the mast-cells! Unfortunately, the in-vitro basophil activation test, which could help to throw more light on some of the difficult cases, is not yet available here. In the past year an ELIZA test for chlorhexidine has become available (ImmunoCap250(R)). The results of this test correspond well with skin-prick testing. After a positive response, patients are warned of chlorhexidine being present in a number of antiseptic creams, medicated soaps and mouth washes. Although intact skin is a good barrier, there have been several reports of contact dermatitis to this antiseptic. References: Beaudouin E et al.Immediate hypersensitivity to chlorhexidine: literature review. Eur Ann Allergy Clin Immunol. 2004 Apr; 36(4):123-6 (PubMed) Autio-Gold J. Oper Dent,2008 Nov-Dec;33(6):710-6 (PubMed) Anderson M H. Calif Dent Assoc. 2003 Mar;31(3):211-4 Krautheim A B et al. Cont. Derm. 2004 May;50(3):113-6 Conflict of Interest:None declared |
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Craig A Patterson, Pharmacist Australian Medicines Handbook
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Notwithstanding the positive skin prick tests to chlorhexidine in the case series described by Parkes et al, another potential culprit for the observed reactions is the preservative used in Instillagel. Hydroxybenzoate ester preservatives are known to cause allergic, often delayed, reactions; immediate hypersensitivity has been reported rarely on injection of parenteral preparations. When hydroxybenzoates are used topically in cosmetics, the incidence of allergic reactions is higher in people with eczema or skin trauma than it is in those with intact skin.(1) Exposure to these preservatives following application of Instillagel to the urethral mucosa could be seen as analogous to application to damaged skin or parenteral administration, eliciting a reaction in sensitive or atopic individuals. (1) Sweetman SC. Martindale: The complete drug reference. 35th ed. Pharmaceutical Press; London 2007 Conflict of Interest:None declared |
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