4,4'-Thiobis(2-tert-butyl-5-methylphenol), an antioxidant in medical devices that may cause allergic contact dermatitis.

BACKGROUND: Antioxidants in medical devices, added to protect polymers or adhesives, may also cause contact dermatitis in some individuals. OBJECTIVES: To present data on sensitization to 4,4'-thiobis(2-tert-butyl-5-methylphenol), an antioxidant detected in some types of medical devices, for six patients that experienced eczematous reactions to different medical devices. METHODS: Patch testing with 4,4'-thiobis(2-tert-butyl-5-methylphenol), 1% pet was performed. Gas chromatography-mass spectrometry (GC-MS) was used for identification of 4,4'-thiobis(2-tert-butyl-5-methylphenol) in different medical device products. RESULTS: Six patients with contact allergy to 4,4'-thiobis(2-tert-butyl-5-methylphenol) also had relevant contact allergic reactions to medical devices containing the antioxidant. The presence of the antioxidant in products was detected using GC-MS analysis. CONCLUSIONS: The antioxidant 4,4'-thiobis(2-tert-butyl-5-methylphenol) may cause allergic contact dermatitis after exposure to different medical devices.

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).

Epoxy allergy, investigation of a modern industry.

BACKGROUND: Five workers from an industry manufacturing various articles from carbon fibre reinforced epoxy plastics were referred to our department because of suspected occupational allergic contact dermatitis (OACD). When patch tested, four of them had positive reactions to components of epoxy resin systems (ERSs) that could explain their current skin problems. All of them had been working at the same workstation at a specially designed pressing machine, with operations including manually mixing epoxy resin with hardener. Multiple cases of OACD in the plant prompted an investigation including all workers with possible risk exposures at the plant. OBJECTIVES: To investigate the prevalence of occupational dermatoses and contact allergies among the workers at the plant. MATERIALS AND METHODS: Totally 25 workers underwent investigation that included a brief consultation with a standardized anamnesis and clinical examination followed by patch testing. RESULTS: ERSs-related reactions were found in 7 of the 25 investigated workers. None of the seven had a history of previous exposure to ERSs and they are regarded as sensitized through work. CONCLUSIONS: Twenty-eight percent of investigated workers showed reactions to ERSs. Of these the majority would have been missed if supplementary testing would not have been added to testing with the Swedish base line series.

Simultaneous patch testing with fragrance markers in the baseline series and the ingredients of fragrance mixes: An update from southern Sweden.

BACKGROUND: Regularly updating the prevalence of fragrance contact allergy (CA) is important. Patch testing with fragrance markers in the baseline series and the ingredients of fragrance mixes (FMs) is still debated. OBJECTIVES: To update the prevalence and clinical characteristics of patients with fragrance CA. To establish the results of patch testing with individual allergens of FMs. METHODS: A retrospective analysis of 3539 patients with dermatitis who were patch tested with the baseline series and FMs ingredients during 2016 to 2020 was performed. RESULTS: The prevalence of fragrance CA was 13%. About 10% of these patients with fragrance CA would be missed if the individual ingredients were not tested. Unlike hydroxyisohexyl 3-cyclohexene carboxaldehyde, there was no decreasing trend of CA to Evernia prunastri (oakmoss) extract after the EU regulation came into force. Patients with CA from only one ingredient of the mixes or having a weak positive reaction to the ingredients were significantly missed when tested with only the fragrance markers in the baseline series. CONCLUSIONS: Patch testing with individual fragrance allergens is crucial for experts to expand knowledge in the fragrance CA field. The concentrations of the allergens in FMs may need to be adjusted to detect patients with fragrance CA, since some were significantly overlooked.

Further Evidence of Allergic Contact Dermatitis Caused by 2,2'-Methylenebis(6- tert -Butyl-4-Methylphenol) Monoacrylate, a New Sensitizer in the Dexcom G6 Glucose Sensor.

BACKGROUND: Since the spring of 2020, we have seen several patients experiencing severe allergic contact dermatitis (ACD) from the Dexcom G6 glucose sensor after the composition of the sensor's adhesive patch had been changed. We have previously reported the finding of a new sensitizer, 2,2'-methylenebis(6- tert -butyl-4-methylphenol) monoacrylate, in the Dexcom G6 adhesive patch. Three patients with ACD from Dexcom G6 tested positive to this sensitizer. They were also allergic to isobornyl acrylate, a sensitizer present both in Dexcom G6 and in other medical devices previously used by these patients. OBJECTIVE: The aim of the study was to report the first 4 cases sensitized to 2,2'-methylenebis(6- tert -butyl-4-methylphenol) monoacrylate without a simultaneous allergy to isobornyl acrylate. METHODS: The cases were patch tested their own materials, a medical device series, and 2,2'-methylenebis(6- tert -butyl-4-methylphenol) monoacrylate in several concentrations. RESULTS: All 4 cases tested positive to 2,2'-methylenebis(6- tert -butyl-4-methylphenol) monoacrylate at either 1.0% or 1.5% in petrolatum, whereas 20 controls tested negative to both concentrations. CONCLUSIONS: The cases reported here provide further evidence of 2,2'-methylenebis(6- tert -butyl-4-methylphenol) monoacrylate as a relevant culprit sensitizer in patients with ACD from Dexcom G6. However, the initially used patch test concentration (0.3%) did not suffice to elicit positive reactions in these cases, which is why patch testing at 1.5% is recommended.

Contact allergy to oxidized linalool and oxidized limonene: Patch testing in consecutive patients with dermatitis.

BACKGROUND: Contact allergy to oxidized (ox.) linalool and ox. limonene has been reported to have a high prevalence, raising the question of inclusion into the baseline series. However, several important issues should be clarified and further investigated before inclusion can be warranted. OBJECTIVES: To report the trends of ox. terpenes allergy in patients with dermatitis, features of the patch test reactions, and clinical characteristics of the patients. METHODS: A retrospective analysis of 5773 patients was performed. All patients were patch tested with baseline series, individual ingredients of fragrance mix I and II, ox. linalool, and ox. limonene from 2013 to 2020. RESULTS: The prevalence rates of contact allergy to ox. linalool and ox. limonene were 7.0% and 5.1%, respectively. Significantly increasing trends of contact allergy were observed. More than 95% of contact allergy cases were identified on Day 3/4. Patients with contact allergy to ox. linalool and ox. limonene were significantly younger than those with contact allergy to other fragrances and were predominantly female. Strong reactions were associated with older age and multiple fragrance allergies. CONCLUSIONS: Contact allergy to ox. linalool and ox. limonene is becoming increasingly important, and findings show intriguing features. More studies concerning the clinical relevance before recommending these substances for screening are required.

Changes in adhesive ingredients in continuous glucose monitoring systems may induce new contact allergy pattern.

BACKGROUND: Medical devices (MD) in close skin-contact for a prolonged time, such as glucose monitoring (CGM) systems, are a risk factor for contact allergy, and there has been an increase in patients using these. Correct diagnosis demands targetted testing. OBJECTIVES: We report a new allergen in a continuous CGM system in which the adhesive was changed. The allergy pattern of the patients diagnosed is reported. METHODS: The three patients reported were patch tested with an MD series, own material, and possible allergens found through analysis with gas chromatography-mass spectrometry, comparing analysis from the CGM system before and after change. RESULTS: The patients were sensitized to isobornyl acrylate (IBOA), found in previously used devices and the present CGM. Apart from IBOA, the culprit allergen was found to be 2,2'-methylenebis(6-tert-butyl-4-methylphenol) monoacrylate. CONCLUSION: Allergic contact dermatitis due to CGM systems and insulin pumps are difficult to investigate and require chemical analysis. Because of the lack of information on substances used in the production, and when changes with MDs are initiated, it is difficult to advise patients, especially since they risk sensitization to several allergens. The use of MDs has increased and, thus, the need for collaboration between manufacturers, clinicians, and patient organizations.

Contact allergy to polyhexamethylene biguanide (polyaminopropyl biguanide).

BACKGROUND: Polyaminopropyl biguanide (INCI name) and polyhexamethylene biguanide (PHMB) are polymeric biguanides. PHMB is a broad-spectrum antimicrobial substance used as a preservative in many products. Due to our limited knowledge on PHMB contact allergy frequency and the fact that cases of allergic contact dermatitis to PHMB might be missed, we have included PHMB as a screening allergen since 2016. OBJECTIVE: To report the prevalence of positive patch test reactions to PHMB as a screening allergen in patients with suspected allergic contact dermatitis. METHODS: A retrospective analysis of 1760 patch tested patients from July 2016 to December 2018 was performed. Polyaminopropyl biguanide 2.0% aqua was included in the extended Malmö baseline series during the study period. RESULTS: Of all patients, 1204 (68.4%) were female. Positive patch test reactions were reported in 19 patients (1.1%). The most common sites of lesions were face, head, and neck (52.6%). There was a significant correlation between concomitant reactions to PHMB and other cosmetic-related allergens. CONCLUSION: The prevalence of positive reactions to PHMB was higher than that previously reported. Patch testing with PHMB should be performed in patients with dermatitis who have lesions on the face, head, and neck.

Skin application of glutathione and iron sulfate can inhibit elicitation of allergic contact dermatitis from hexavalent chromium.

BACKGROUND: Allergic contact dermatitis (ACD) caused by hexavalent chromium, Cr(VI), is often severe and difficult to treat. The most common source of exposure to Cr(VI) in Sweden used to be cement, and more recently leather. The contact allergy can be diminished or inhibited if the exposure is decreased or ceases. Barrier creams against different kinds of allergens have been investigated for their protective properties which may offer protection against Cr(VI) exposure. OBJECTIVES: To investigate the capacity of formulas containing glutathione (GSH) and iron sulfate to inhibit elicitation of ACD in Cr(VI)-allergic individuals when exposed to Cr(VI). METHODS: In 18 Cr(VI)-allergic volunteers the back was divided into eight patch test areas which were treated with preparations of possible barrier creams, prior to patch testing with a dilution series of potassium dichromate and a buffered extract of cement. RESULTS: A significant reduction in reactivity to Cr(VI) and cement extract on skin treated with formulas containing GSH or iron sulfate was noticed, compared with untreated skin. CONCLUSION: Formulas containing GSH or iron sulfate in barrier creams inhibit ACD in individuals allergic to Cr(VI) when applied before exposure to Cr(VI) and cement extract.

Can reducing cosmetic substances help prevent chromate contact allergy?

BACKGROUND: Allergic contact dermatitis caused by Cr(VI) is often severe and difficult to treat. Therefore, primary prevention is a main goal but, secondary prevention can be valuable to ease the symptoms or prevent relapse of Cr(VI) dermatitis when sensitization has occurred. Barrier creams have been tried for many chemical substances, but until now there is no successful barrier cream against Cr(VI). OBJECTIVES: To investigate the ability of reducing agents to transform Cr(VI) into Cr(III) in an experimental situation, in order to find suitable chemicals to investigate for possible use in a barrier cream. METHODS: The capacity to reduce the amount of Cr(VI) was analyzed in water solutions of acetylcysteine, cysteine, dihydroxyacetone, glutathione, and iron sulfate heptahydrate. Thereafter the reducing capacity of acetylcysteine, dihydroxyacetone, glutathione, and iron sulfate on the amount of Cr(VI) in cement extracts was investigated. The content of Cr(VI) in the test solutions and in the cement extracts was estimated by the diphenyl carbazide spot test. RESULTS: All of the chosen chemicals reduced the amount of Cr(VI) in the test solutions and in the cement extracts to some extent. The reducing capacity was most prominent for iron sulfate. CONCLUSION: A reducing capacity was found for all chosen chemicals.

A retrospective investigation of hexavalent chromium allergy in southern Sweden.

BACKGROUND: Historically, allergic contact dermatitis caused by hexavalent chromium [Cr(VI)] in cement was the most common cause of invalidity attributable to skin disease in Sweden. Since the legislation to reduce Cr(VI) in cement was introduced in 1989, we rarely see allergic contact dermatitis caused by cement. OBJECTIVES: To examine the frequency of contact allergy to Cr(VI) in southern Sweden in 2005-2014. METHODS: We investigated the occurrence of positive reactions to potassium dichromate 0.5% pet. in consecutively tested dermatitis patients, and compared the occurrence of atopic dermatitis, localization of dermatitis and simultaneous positive reactions to cobalt chloride and nickel sulfate in the Cr(VI)-positive patients with those in a group of patients with a similar age and sex distribution. RESULTS: In total, 6482 patients were tested, and 233 Cr(VI)-allergic individuals were found (3.6%). A significantly higher proportion of atopic dermatitis was found among Cr(VI)-allergic patients, and a significantly higher share of foot dermatitis was found among Cr(VI)-allergic women, than among controls. Cr(VI) allergy was less likely when both nickel allergy and cobalt allergy were present. CONCLUSION: A relatively high frequency of contact allergy to Cr(VI) was found. The cause has shifted from cement exposure to other exposures, probably mainly leather.