It is not always chlorhexidine: Identification of benzoxonium chloride and lauramine oxide as culprit allergens in a popular antiseptic in Switzerland.

BACKGROUND: A popular antiseptic spray in Switzerland (Merfen spray), containing chlorhexidine digluconate, benzoxonium chloride and lauramine oxide, is frequently used to treat skin wounds. However, it is also increasingly reported as a major cause of adverse skin reactions, including allergic contact dermatitis (ACD). OBJECTIVES: To investigate the contact allergens responsible for ACD from this antiseptic. PATIENTS/METHODS: Patch tests were performed on seven patients with a clinical history compatible with contact dermatitis from this antiseptic mixture. RESULTS: All patients presented with acute eczematous reactions following contact with either Merfen spray alone, or with multiple products including this spray. Patients showed positive reactions to this product in both patch tests and repeated open application tests (ROATs). Four patients showed dose-dependent reactions to both benzoxonium chloride and lauramine oxide. One patient showed a dose-dependent reaction to the former and a non-dose-dependent reaction to the latter. Finally, two subjects showed responses only to lauramine oxide. One patient reacted to chlorhexidine digluconate 0.5% aq. in addition to both other allergens. CONCLUSIONS: Two commercially unavailable allergens, that is, benzoxonium chloride and/or lauramine oxide were identified as major causes of ACD from Merfen antiseptic spray, whereas chlorhexidine digluconate was a contributing culprit in only one patient.

Isocyanates may contribute to allergic contact dermatitis from diabetes devices and wound dressings.

BACKGROUND: Isocyanates are well-known occupational allergens, but can also be present in medical devices. OBJECTIVES: To highlight that contact sensitization to isocyanates might contribute to allergic contact dermatitis (ACD) from polyurethane (PU)-containing diabetes devices and wound dressings. PATIENTS AND METHODS: Nineteen patients with suspected ACD from diabetes devices and/or wound dressings were patch tested to an isocyanate series. Four wound dressings, six diabetes devices and four monomeric isocyanate patch test preparations were analysed with gas chromatography - mass spectrometry. RESULTS: Eight patients reacted to isocyanates and corresponding amines: 3 to isophorone diisocyanate (IPDI), 4 to 4,4'-diaminodiphenylmethane (MDA), 4 to 2,4-toluene diisocyanate (TDI) and 1 to polymeric methylene diphenyl diisocyanate (PMDI). Three of four wound dressings contained isocyanates (methylene diphenyl diisocyanate [MDI], TDI and/or IPDI), whereas five of six diabetes devices contained 4,4'-MDI, and one of them also IPDI. None of the medical devices contained 1,6-hexamethylene diisocyanate. Contrary to IPDI, and especially MDI, only the concentration of the TDI patch test preparation corresponded approximately (80%) to its label. CONCLUSION: Patch tests with isocyanates may be worth-while in patients with suspected ACD from PU-containing medical devices. Besides MDA, and PMDI, also TDI might potentially be a marker for MDI-sensitization.

Allergic contact dermatitis from ("hypoallergenic") adhesives containing D-limonene.

BACKGROUND: Besides being a potential component of (some species of) colophonium, D-limonene is also used as a tackifier in the production of adhesives. Hydroperoxides of limonene are well-known skin sensitizers. OBJECTIVES: To show that D-limonene may be present in colophonium-containing but also colophonium-free ("hypoallergenic") adhesives, and that patients suffering from allergic contact dermatitis (ACD) from both types of adhesives might display positive patch test reactions to limonene hydroperoxides in this regard. METHODS: Five patients with suspected ACD from adhesives were patch tested to the baseline series (containing limonene hydroperoxides 0.3 and 0.2% pet.), additional series and, if available, to the culprit adhesives. The adhesives labelled as containing colophonium (n = 3) or free from it (n = 2) were analysed with gas chromatography - mass spectrometry (GC-MS) for the presence of D-limonene. RESULTS: All five patients sensitised to adhesives had (strong) positive patch test reactions to limonene hydroperoxides. The presence of D-limonene, and/or related components, could be demonstrated in all three colophonium-containing and, surprisingly, also in two colophonium-free ("hypoallergenic") tapes. CONCLUSIONS: D-limonene may be present in both regular and "hypoallergenic" adhesives, with limonene hydroperoxides potentially contributing to ACD from such medical devices. The use of fragrance chemicals in adhesives deserves further research.

Allergic contact dermatitis from potassium sorbate and sorbic acid in topical pharmaceuticals and medical devices.

BACKGROUND: The preservatives sorbic acid (SA) and potassium sorbate (PS) are considered rare skin sensitizers. PS-containing products always contain SA to a certain extent, and positivity to PS may reflect sensitization to SA. Their optimal patch-test conditions are unknown. OBJECTIVES: To report on the outcome of testing with SA and PS in various concentrations and/or vehicles. PATIENTS AND METHODS: Seventeen patients with allergic contact dermatitis from PS/SA-containing topical pharmaceuticals and medical devices were patch tested to SA 2% and 5% pet.; SA 1%, 2%, 3%, 5%. eth.; and/or SA 2% aq., whereas PS was patch tested 5% pet. and/or 5% aq. RESULTS: Only one patient, not tested to the ethanol preparations, presented with a (doubtful) positive reaction to SA 2% pet., while this remained negative in 13 patients who reacted to SA 2% eth. The preparations containing SA 5% pet.; 1%, 3%, and 5% eth.; and SA 2% aq. had little or no additional value. PS 5% pet. performed better than 5% aq., and always mirrored SA sensitization. CONCLUSIONS: Sensitization to SA and PS is probably underestimated. SA 2% eth. and PS 5% pet. are preferred for patch testing, and patients sensitized to SA should avoid PS-containing products. HIGHLIGHTS: Potassium sorbate (PS) and sorbic acid (SA) are widely used preservatives. PS-containing products always contain some SA. Both are considered rare skin sensitizers, but contact allergy in response to them might be underestimated. SA 2% eth. and PS 5% pet., rather than SA 2% pet. and PS 5% aq., respectively, may be required to diagnose contact allergy from PS/SA-containing topical pharmaceuticals and medical devices. A positive patch test to PS reflects sensitization to SA, and patients sensitized to SA should also avoid PS-containing products.

Concomitant positive patch test reactions in FreeStyle-allergic patients sensitized to isobornyl acrylate.

BACKGROUND: Concomitant positive patch test reactions in patients sensitized to isobornyl acrylate (IBOA) have rarely been documented. OBJECTIVES: To report concomitant sensitizations in patients with allergic contact dermatitis (ACD) from the glucose sensor FreeStyle Libre and sensitized to IBOA. METHODS: In 2019, 26 patients with suspected ACD from FreeStyle Libre were patch tested to a baseline series and to a (meth) acrylate series containing IBOA and 2-phenoxyethyl acrylate (PEA) 0.1% pet. Diabetes devices and patch test preparations were analyzed with gas chromatography - mass spectrometry (GC-MS) for the presence of IBOA and PEA. RESULTS: Of the 26 patients, 18 (69%) were sensitized to IBOA, and eight (44%) and 11 (61%) of these were co-sensitized to sesquiterpene lactones and fragrances, respectively. Ten patients (56%) were co-sensitized to PEA, which, contrary to IBOA, could not be detected in any device. The PEA test material was shown to be contaminated with IBOA. CONCLUSIONS: Contact allergy to IBOA appears to be declining and IBOA-sensitized patients are most often co-sensitized to sesquiterpene lactones and fragrances. Vigilance is required when patch testing (acrylate) materials obtained from industry, as these might be contaminated and, hence, alter the results and their interpretation.

The presence of benzophenone in sunscreens and cosmetics containing the organic UV filter octocrylene: A laboratory study.

BACKGROUND: The reason why patients photosensitized to the drug ketoprofen (KP) may develop severe photoallergic skin reactions to octocrylene (OCT), an organic ultraviolet filter in sunscreens and cosmetics, remains largely unknown. OCT can be synthesized by using unsubstituted benzophenone (BP), a possible human carcinogen. OBJECTIVES: To verify if, and to what extent, BP residues are present in OCT-containing consumer products. METHODS: The raw material of OCT and 39 skincare products, of which 28 contain OCT, were chemically analysed for the presence of BP by means of liquid chromatography. RESULTS: In the OCT raw material and in all 28 OCT-containing products the presence of BP could be demonstrated, mostly in concentrations above 10 ppm (0.001%), whereas a majority of OCT-free products (8/11, 73%) did not contain BP. Moreover, BP concentrations significantly increased, in a time- and temperature-dependent manner, likely due to the additional degradation of OCT. CONCLUSIONS: Photoallergic contact dermatitis from OCT in patients photosensitized to KP might rely on residual BP impurities. Toxicological and ecological studies that evaluate the safety of OCT might also need to consider the concomitant presence of BP.

Concomitant contact-allergic reactions to iodopropynyl butylcarbamate and iodine.

BACKGROUND: Iodopropynyl butylcarbamate (IPBC) is a broad-spectrum preservative for use in several product types, including cosmetics, in which its concentrations have been limited by EU legislation because of concerns related to its iodine content and release, and the risk of subsequent iodine overdose. OBJECTIVES: To report on concomitant patch test reactions observed with iodine and IPBC in patients sensitized to iodine-containing antiseptics. PATIENTS: Between 2012 and 2018, seven patients, six from Belgium and one from France, two suffering from acute dermatitis during surgical interventions, four from dermatitis caused by wound treatment, and one from occupational dermatitis, were shown to be sensitized to iodine and/or povidone-iodine (PVP-I), which was considered to be relevant for their dermatitis. All patients were coincidentally also patch tested with IPBC. RESULTS: All patients showed positive patch test reactions to several other allergens, including IPBC. No relevance could be detected for IPBC. CONCLUSIONS: We suspect that, notwithstanding the absence of firm evidence for IPBC being dehalogenated to produce free iodine in animals or in humans, the patch test reactions to IPBC in iodine-allergic subjects were possibly caused by free iodine released from this preservative agent, thus underlining the EU restrictions regarding the use of this preservative in cosmetics.