IgE‐mediated chlorhexidine allergy—Cross‐reactivity with other biguanide disinfectants

Mueller‐Wirth, Nicole; Buenter, Antonia; Jörg, Lukas; Ebo, Didier G.; Glatz, Martin; Fernando, Suran L.; Spoerl, David; Helbling, Arthur; Hausmann, Oliver; Gupta, Nisha; Pichler, Werner J. (2020). IgE‐mediated chlorhexidine allergy—Cross‐reactivity with other biguanide disinfectants. Allergy, 75(12), pp. 3237-3247. Wiley-Blackwell 10.1111/all.14497

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Background: Chlorhexidine (CHX) is a widely utilized disinfectant that can cause IgE-mediated urticaria/anaphylaxis. The cross-reactivity of patients with IgE-mediated CHX allergy with other disinfectants, which share structural similarities with CHX like polyhexanide (polyhexamethylene biguanide; PHMB), alexidine (ALX), or octenidine (OCT), is unknown.
Methods: Forty-four patients with anaphylaxis or urticaria upon CHX exposure and positive skin prick test (SPT) and/or positive CHX ImmunoCAP test (Phadia TFS, Uppsala, Sweden) were recruited. IgE to the biguanide and/or hexamethylene structure was investigated with PHMB ImmunoCAP (n = 32) and by basophil activation tests (BAT) with CHX and ALX (n = 37). Inhibition tests of CHX and PHMB ImmunoCAPs by CHX, ALX, PHMB, and OCT were performed.
Results: IgE reactivity to PHMB as surrogate marker for biguanide/hexamethylene reactivity was detected in 5/32 sera. Seven of 37 patients showed a positive BAT with ALX, but only under optimized conditions. Binding to CHX ImmunoCAP was inhibited by ALX in 1/32 sera, and binding to PHMB was blocked by ALX (1/5) and by OCT in another (1/5). In SPT, 9/10 patients were positive for CHX and 3 of them with ALX (only at highest concentration at 5 mg/mL). A further patient reacted primarily with OCT and showed IgE cross-reactivity with CHX, ALX, and PHMB.
Conclusion: The IgE response to CHX seems polyclonal. The chloroguanide ending of CHX is the main epitope for the IgE and is suitable as screening assay to detect CHX reactivity. IgE-reactivities with the biguanide or hexamethylene components of other disinfectants (ALX, PHMB) can be detected by SPT, PHMB ImmunoCAP, and ALX-BAT in 15%-33% of CHX-allergic patients.

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