A Case of Severe Anaphylaxis to Polyhexanide: Cross-Reactivity between Biguanide Antiseptics.

We present the case of a 77-year-old female patient who suffered from severe anaphylaxis during wound care. Allergologic evaluation yielded specific IgE antibodies to chlorhexidine, but anaphylaxis to chlorhexidine was not congruent with the patient history and dermal provocation tests. However, skin prick tests provided evidence for a sensitization to polyhexanide that was further supported by the detection of specific IgE antibodies to polyhexanide, the results of basophil activation tests and IgE inhibition analysis. We presume cross-reactive IgE antibodies binding to both biguanide antiseptics and identified polyhexanide as the likely cause of the anaphylactic reaction. We recognize polyhexanide as an emerging allergen that has to be considered as a cause of anaphylaxis.

Classification of wounds at risk and their antimicrobial treatment with polihexanide: a practice-oriented expert recommendation.

Currently, there are no generally accepted definitions for wounds at risk of infection. In clinical practice, too many chronic wounds are regarded as being at risk of infection, and therefore many topical antimicrobials - in terms of frequency and duration of use - are applied to wounds. Based on expert discussion and current knowledge, a clinical assessment score was developed. The objective of this wounds at risk (W.A.R.) score is to allow decision-making on the indication for the use of antiseptics on the basis of polihexanide. The proposed clinical classification of W.A.R. shall facilitate the decision for wound antisepsis and allow an appropriate general treatment regimen with the focus on the prevention of wound infection. The W.A.R. score is based on a clinically oriented risk assessment using concrete patient circumstances. The indication for the use of antiseptics results from the addition of differently weighted risk causes, for which points are assigned. Antimicrobial treatment is justified in the case of 3 or more points.

The biocide polyhexamethylene biguanide remains an uncommon contact allergen.

Polyhexamethylene biguanide (PHMB) is used as a preservative in cosmetics and personal care products. Previous studies had shown a frequency of sensitization to PHMB of 0.5% and 0.4% in unselected dermatitis patients. The objective of this study was to determine the current frequency of sensitization to PHMB. From July 2005 until December 2005, a total of 1975 consecutive patients were patch tested with PHMB. 10 patients (0.5%) had positive patch test reactions to PHMB 2.5% aq. (9+ and 1++) and 16 patients (0.8%) to PHMB 5.0% aq. (12 +, and 4 ++). The test reaction pattern (reaction index and positivity ratio) of both preparations and a limited concordance between results from both concentrations (Cohen's kappa = 0.35) are probably indicative of a substantial number of false positive reactions. Potential causal exposures were assessed by a case by case analysis and by referring to surrogate markers of exposure in terms of concomitant reactions. Occupational exposures were identified as a probable cause of sensitization. Further risk factors included leg dermatitis and old age. The frequency of sensitization remains low. It is very unlikely that exposure to cosmetics or personal care products may have played a role in the few cases sensitized.

Anaphylaxis to chlorhexidine. Case report. Implication of immunoglobulin E antibodies and identification of an allergenic determinant.

BACKGROUND: There are many reports of allergic reactions, including anaphylaxis, following exposure to chlorhexidine. Reactions may occur via contact with the skin and mucous membranes or from catheters treated with the antibacterial agent. Apart from implicating chlorguanide in immunoglobulin (Ig) E antibody-binding studies on serum from an anaphylactic patient, little work has been done on the molecular basis of recognition of the agent in sensitive subjects. OBJECTIVES: The molecular basis of IgE-binding to chlorhexidine was closely examined with the view of defining its fine structural recognition features by antibodies from a subject who experienced anaphylaxis following contact with the antiseptic. METHODS: Tryptase determinations, different drug-solid phases, immunoassays and quantitative hapten inhibition studies with chlorhexidine and selected structural analogues were employed together with serum from the anaphylactic patient. Results were analysed to define the complete drug allergenic determinant and to identify the important structural features complementary to the IgE antibody combining sites. RESULTS: The subject's serum tryptase levels sampled after the reaction were elevated and employment of a chlorhexidine-EA Sepharose solid phase showed the presence of serum IgE antibodies to the drug. Lack of inhibition by 4-chlorophenol and other selected substituted phenyl compounds showed that the terminal groups at each end of the chlorhexidine molecule, alone, did not account for antibody recognition of the antibacterial agent. Although chlorguanide and alexidine, the structures of which each comprise part of the chlorhexidine molecule, showed significant inhibition of the binding of IgE antibodies to chlorhexidine, neither compound was as potent an inhibitor as chlorhexidine itself. Two molecules of chlorguanide make up the symmetrical molecule of chlorhexidine while the interior structure of alexidine (that is excluding the terminal 2-ethylhexyl groups) is identical to part of the chlorhexidine molecule. CONCLUSIONS: Taken together, for this patient, these results lead to the conclusion that the whole chlorhexidine molecule is complementary to the IgE antibody combining sites and that the 4-chlorophenol, biguanide and hexamethylene structures together comprise the allergenic determinant. Hence, like one of the trimethoprim determinants identified, but unlike most drug allergenic determinants identified so far, the chlorhexidine allergenic determinant identified here encompasses the entire molecule.

[Resistance to hypoglycemic sulfanilamides and biguanidines and its immune genesis]. / Ustoichivost' k gipoglikemiziruiushchim sul'fanilamidam i biguanidam i ee immunnyi genez.

In blood of patients with diabetes mellitus receiving bucarban or adebit antibodies to these drugs were discovered. Patients medicated with bucarban demonstrated an elevated content of antibodies to insulin. The appearance of specific antibodies occurred in rabbits and rats following introduction of bucarban, glucophage or adebit per se or when mixed with adjuvants. An increased production of antibodies to endogenous insulin was observed in all animals reveiving bucarban. Introduction to rats of inactivated (at 56 degrees C for 30 minutes) serum of patients with diabetes mellitus that contained antibodies to bucarban or adebit as well as immune rabbit sera greatly mitigated the hypoglycemic effect of the latter. Introduction to rats of the blood serum taken in patients reveiving bucarban allso attenuated the effect of exogenous insulin. These findings suggest that, possessing neutralizing properties, these antibodies to bucarban, adebit and glucophage cause habituation to these substances. Accumulation in the blood of autoantibodies to insulin following introduction of bacarban reduces the sensitivity to the exogenous hormone and manifests the existence of an immune mechanism securing the preservation of chemical homeostasis in the organism.