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.

Analysis of Hexavalent Chromium in Cement Samples From Countries Within and Outside the EU: A Study From the International Contact Dermatitis Research Group.

Background: Allergic contact dermatitis (ACD) caused by hexavalent chromium (Cr(VI)) is often severe and difficult to treat. The content of Cr(VI) in cement can be reduced by, for example, addition of iron(II) sulfate. Since 2005 the content of Cr(VI) in cement is regulated in the EU Directive 2003/53/EC and must not exceed 2 ppm. Since this regulation came into force, ACD caused by cement has markedly been reduced. Objective: To investigate Cr(VI) and total chromium content in samples of cement from countries within and outside the EU. Methods: The members of the International Contact Dermatitis Research Group (ICDRG) were invited to participate in the study with the aim to collect cement samples from geographically different areas. The content of Cr(VI) in the samples was estimated by the diphenyl carbazide spot test, atomic absorption spectroscopy was used to assess the total chromium content. Results: Forty-five cement samples were analyzed, containing amounts of Cr(VI) from <0.1 to >70 ppm. Twenty-one samples contained >2 ppm Cr(VI), 24 contained less. Four of 17 samples from within the EU contained >2 ppm Cr(VI), that is, higher amounts than stipulated in the EU directive, as compared with 17 samples from countries outside the EU. Conclusion: In countries outside the EU, significantly more cement samples contained >2 ppm Cr(VI).

Contact allergy to and allergic contact dermatitis from formaldehyde and formaldehyde releasers: A clinical review and update.

This review aims to provide a clinically useful update regarding the role of formaldehyde (FA) and its five main releasers (FRs) quaternium-15, diazolidinyl urea, DMDM hydantoin, imidazolidinyl urea, and 2-bromo-2-nitropropane-1,3-diol (bronopol) in contact allergy and allergic contact dermatitis. These ubiquitous preservatives are still often present, and sometimes undeclared, in cosmetics, pharmaceuticals, medical devices, household detergents, and chemical (industrial) products. In Europe, the use of free FA and quaternium-15 in cosmetics is forbidden and contact allergy rates have been found to be stable to decreasing. However, FA/FRs still readily provoke localized (eg, facial/hand), airborne, and generalized dermatitis, and may also complicate atopic and stasis dermatitis, or result in nummular dermatitis. Seborrheic-, rosacea- and impetigo-like dermatitis have recently been reported. For a correct diagnosis, FA 2% aq. (0.60 mg/cm2 ) should be used, and particularly the FRs bronopol 0.5% pet. and diazolidinyl urea 2% pet. should be patch tested separately in a baseline series. If sensitization to FA occurs, both FA and FRs should preferably be avoided, except perhaps for bronopol in case it tests negatively. If a patient reacts to one or more FRs (such as bronopol or diazolidinyl/imidazolidinyl urea), but not to FA, then the specific FR(s) should be avoided.

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.

Contact allergy in a paediatric population observed in a tertiary referral centre in Belgium.

BACKGROUND: Contact allergy is increasingly recognized as being important in children with eczema. OBJECTIVES: To retrospectively analyse the patch test results in children over the past 10 years, aiming to (1) evaluate demographic characteristics and lesion locations, (2) describe frequencies of positive patch test reactions, and (3) investigate the relationship with atopic dermatitis (AD). METHODS: A total of 329 children were patch tested between January 2010 and December 2019 with the European (children) baseline series and/or other series, and the personal product(s) used. RESULTS: A total of 119 (36%) children presented with at least one positive reaction. Children with AD had a higher prevalence of positive reactions compared with the non-AD group (P = .002), but without statistically significant difference regarding sensitization to more than one hapten (P = .39). The face (20.2%), hands (19.3%), feet (16.8%), arms (12.6%), and body folds (10.9%) were the most common sites of primary localizations. The most frequent contact allergens were nickel sulfate and linalool hydroperoxide (both 16%), limonene hydroperoxide (13.5%), and para-phenylenediamine (10.9%). No statistically significant difference for nickel sulfate was found between the AD and non-AD group (P = .20). CONCLUSIONS: Contact allergy in children with eczema was frequently observed in our tertiary referral centre in Belgium as well, confirming the need for patch testing.

Evolution of methylisothiazolinone sensitization: A Belgian multicentric study from 2014 to 2019.

BACKGROUND: In the 2010s an epidemic of allergic contact dermatitis to methylisothiazolinone (MI) occurred in Europe. European authorities banned the use of methylisothiazolinone in leave-on cosmetics in 2017 and limited its use in rinse-off products in 2018. OBJECTIVES: To investigate the sensitization rate to MI in Belgium between January 2014 and December 2019, and to assess cosensitizations to octylisothiazolinone (OIT) and benzisothiazolinone (BIT) in MI-sensitized patients. METHODS: A retrospective study of patch test results with MI, OIT, and BIT observed in patients attending five Belgian hospitals. RESULTS: Overall, 560 of 10 029 patients (5.58%) had a positive patch test reaction to MI, and its sensitization rate decreased from 7.9% in 2014 to 3.1% in 2019. Rinse-off cosmetics, paints, and detergents were the most prevalent sensitization sources in recent years. Simultaneous reactions readily occurred to OIT, and, surprisingly, and increasingly, also to BIT. CONCLUSIONS: Contact allergy to MI in Belgium has reached a pre-epidemic level, reflecting the impact of recent regulatory measures. Leave-on cosmetics, in contrast to rinse-off products, have almost disappeared as sensitization sources in Europe. Paints and detergents also remain problematic. The remarkably high number of patients (co)sensitized to BIT should be a focus of future research.

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.

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.

Patch Testing With a New Composition of the Mercapto Mix-A Multicenter Study from the International Contact Dermatitis Research Group.

BACKGROUND: Mercaptobenzothiazole compounds are associated with allergic contact dermatitis caused by rubber products. Several screening substances have been used for patch testing. OBJECTIVE: To compare the frequency of positive test reactions to a mercapto mix containing a higher concentration of 2-mercaptobenzothiazole with reactions to the combination of 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0%. METHODS: There were 7103 dermatitis patients in 12 International Contact Dermatitis Research Group dermatology departments who were patch tested with 2-mercaptobenzothiazole 2.0% petrolatum (pet.), mercapto mix 2.0% pet., and mercapto mix 3.5% pet. RESULTS: Contact allergy to the 3 test preparations varied among the 12 centers: 2-mercaptobenzothiazole 2.0% pet. (0-2.4%), mercapto mix 2.0% pet. (0-4.9%), and mercapto mix 3.5% pet. (0-1.4%). 2-Mercaptobenzothiazole 2.0% and mercapto mix 2.0% detected a few more positive patients compared with mercapto mix 3.5%, but the difference was statistically insignificant (mercapto mix 2.0% pet., P = 1.0; 2-mercapto-benzothiazole 2.0% pet., P = 0.66). CONCLUSIONS: Mercapto mix 3.5% pet. is not better than 2-mercaptobenzothiazole 2.0% and mercapto mix 2.0% by a difference that is significant. By using only 1 test preparation (mercapto mix 3.5%), an additional hapten could be tested. No cases of suspected/proven patch test sensitization were registered.

Patch Testing With Methylchloroisothiazolinone/Methylisothiazolinone Using a New Diagnostic Mix-A Multicenter Study From the International Contact Dermatitis Research Group.

BACKGROUND: In the early 1980s, a preservative containing a mixture of methylchloroisothiazolinone (MCI) and methylisothiazolinone (MI) in a ratio of 3:1 was introduced. This mixture (mix) has been patch tested at 100 ppm (0.01%) worldwide and at 200 ppm (0.02%) in Sweden since 1986 and also in the European baseline series since 2014. OBJECTIVE: A new aqueous mix of MCI 0.015% and MI 0.2% was compared with patch testing with the 2 aqueous baseline preparations of MCI/MI 0.02% and MI 0.2%. METHODS: Four thousand three hundred ninety-seven patients with dermatitis in 12 International Contact Dermatitis Research Group dermatology departments from 3 continents were patch tested simultaneously with the 3 preparations. RESULTS: The frequency of positive patch tests to the allergens varied between 0% and 26.7% in the 12 test centers. The new mixture MCI/MI 0.215% in aqua (aq) detected significantly more patients with MCI/MI allergy than both MCI/MI 0.02% aq (P < 0.001) and MI 0.2% aq (P < 0.001) alone and combined. CONCLUSIONS: The results favor replacing the preparations MCI/MI 0.02% aq and MI 0.2% aq with the mixture MCI/MI 0.215% aq in the International Contact Dermatitis Research Group baseline series.

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.

Iatrogenic allergic contact dermatitis in the (peri)anal and genital area.

BACKGROUND: Allergic contact dermatitis (ACD) from topical medication often occurs in occluded areas, for example, with wound treatment, but also in certain body locations, such as the anogenital area. OBJECTIVES: To investigate the demographics and specific lesion location of patients with ACD from topical drugs applied onto the (peri)anal/genital area, and to identify the respective causal topical pharmaceutical products and ingredients involved. METHODS: From January 2000 to December 10, 2018, 532 patients were tested with the baseline series, sometimes with additional series, and the topical medication used along with the ingredients. The relevant data were extracted from our electronic databases developed in-house. RESULTS: Forty-four patients (9%) out of 473 patients suffering from lesions in the (peri)anal/genital area had positive patch test results to topical drug preparations and/or their ingredients, sometimes in association with cosmetics for intimate hygiene. The most frequent sensitizing active principles were local anaesthetics and corticosteroids, while wool alcohols and to a minor extent benzoic acid were the most frequent culprits among the vehicle components and preservative agents, respectively. CONCLUSIONS: The local conditions (eg, occlusion, sweating, moist) in the anogenital area may favour skin sensitization to topical medication used to treat various skin diseases.