Commonly used antiseptic agent, rare cause of anaphylaxis
We report a case of anaphylaxis attributed to the chlorhexidine component of Instillagel, presenting after a urological procedure, leading to him becoming unconscious and hypotensive.
Authors: Dr P Williams, Dr A Alkali, Department of Dermatology, University Hospital Aintree, Liverpool.
Corresponding Author: Dr P Williams, Department of Dermatology, University Hospital Aintree, Liverpool. E-mail: [email protected]
Anaphylaxis to chlorhexidine is rare. We report a case of anaphylaxis attributed to the chlorhexidine component of Instillagel, presenting after a urological procedure, leading to him becoming unconscious and hypotensive. Urologists should be aware that urethral lubricants may contain chlorhexidine that can trigger anaphylaxis in susceptible individuals. Anaphylaxis should be considered a possible diagnosis when a patient collapses after a routine procedure. Investigation of suspected anaphylactic reactions is important to try and identify a likely trigger for a reaction and to help prevent further exposure and potential harm.
A 71 -year old gentleman with transitional cell carcinoma of the bladder underwent a cystoscopy as part of his surveillance at our hospital. Past medical history included venous eczema only.
Intra-urethral instillagel® (containing lidocaine hydrochloride, chlorhexidine digluconate, methyl-4-hydroxybenzoate and propyl-4-hydroxybenzoate) was administered at the beginning of the procedure prior to urethral dilatation. The intra-operative procedure was entirely uneventful.
He was taken to the recovery room where he was noted to have an urticarial rash. Fifteen minutes later, he became unconscious with a blood pressure of 70/50mmHg.There was no bronchospasm, laryngospasm and no fever. He was diagnosed with anaphylaxis and he was given Intravenous chlorpheniramine, 200mg of iv hydrocortisone and colloids. He made a good recovery.
Reviewing his past medical history, he had developed an urticarial rash three months prior to this after having an identical procedure.
He subsequently had skin prick testing for lidocaine, chlorhexidine, instillagel®, gentamicin, latex and tropical fruits. All were negative apart from a 9.5mm positive result for chlorhexidine. No allergic antibodies to latex were detected and his mast cell tryptase levels were normal.
Chlorhexidine is a synthetic cationic bisbiguanide that was first introduced as a disinfectant and antiseptic in 1954. It is also found in many commercially available products including mouthwashes, antiseptic creams and disinfectant solutions.
Chlorhexidine products are increasingly being recommended for dental hygiene, periodontal care, and implant surgery. Savacol® is frequently used by dental surgeons. The concentrated solution contains 2 mg/ml but when appropriately diluted, it becomes a 0.2% solution of chlorhexidine as a dental wash.
Chlorhexidine is also present in potentially hidden forms, such as a bactericidal coating for central venous catheters or as a component of urethral lubricants. Instillagel®® contains chlorhexidine 0.25%, lidocaine 2%, methyl hydroxybenzoate 0.06%, and propyl hydroxybenzoate 0.025% formulated as a gel; it is a commonly used antiseptic and anaesthetic lubricant. The Summary of Product Characteristics relating to Instillagel® advises against its use in individuals with known hypersensitivity to chlorhexidine, but only the lidocaine component is described as causing undesirable effects(1).
These ubiquitous applications of chlorhexidine raise the possibility of sensitization in a large proportion of the general population (2).Various types of hypersensitivity reactions to chlorhexidine have been described, including: contact dermatitis, photosensitive dermatitis, fixed drug eruption, contact urticaria, occupational asthma, and immediate hypersensitivity reactions such as severe anaphylactic shock, which is a rare but life-threatening complication (3). Life-threatening reactions are generally associated with mucosal exposure (1). Chlorhexidine may cause anaphylaxis by the mucosal route at a much lower concentration than elsewhere, generally as low as 0.05% (4, 5)
Interestingly, serum mast cell tryptase is not always raised in an anaphylactic reaction (as in our patient) as this may be due to an immediate basophilic response. Basophils are circulating blood cells that contain virtually no tryptase; in contrast, tryptase-rich mast-cells are present mainly in connective tissue and mucosae. An ELISA test for chlorhexidine has become available (ImmunoCap250®). The results of this test correspond well with skin-prick testing (2).
Application of chlorhexidine to the mucous membranes can cause severe anaphylactic reactions. Hypersensitivity to chlorhexidine is rare, but its potential to cause anaphylactic shock during hospital procedures is likely to be underestimated. We suggest that chlorhexidine should be used with caution and that it should routinely be considered as a causative agent in unexplained fatal reactions associated with medical procedures.
1. Instillagel®—Summary of Product Characteristics (2000) Clini-Med Ltd.
2. Jayathillake A, Mason DF, Broome K. Allergy to chlorhexidine gluconate in urethral gel: report of four cases and review of the literature. Urology 2003; 61: 837
3. Ebo DG, Bridts CH, Stevens WJ. Anaphylaxis to a urethral lubricant: chlorhexidine as the ‘‘hidden’’ allergen. Acta Clin Belg 2004; 59: 358-60
4. Wicki J, Deluze C, Cirafici L, Desmeules J. Anaphylactic shock induced by intraurethral use of chlorhexidine. Allergy 1999; 54: 768-9.
5. Parkes AW, Harper N, Herwadkar A, Pumphrey R. Anaphylaxis to the chlorhexidine component of Instillagel®: a case series. Br J Anaesth. 2009 Jan;102(1):65-8.
Date added to bjui.org: 30/06/2011