Patterns of simultaneous contact allergies in patients with contact sensitization to oxidised linalool and oxidised limonene.

BACKGROUND: Contact allergy rates of linalool and limonene hydroperoxides (HPs) have increased. OBJECTIVES: To demonstrate the patterns of simultaneous positive patch test (PT) reactions and prevalences of multiple contact allergies (MCAs) in patients with contact allergy to linalool and/or limonene HPs. METHODS: A retrospective analysis of consecutive dermatitis patients in 2015-2020 was performed. RESULTS: Of all 4192 patients, 1851 had at least one positive PT reaction. Of these, 410 (22.2%) had MCAs, significantly related to a higher age (p-value = 0.003). Patients with an exclusively positive reaction to linalool HPs but not limonene HPs were shown to have MCAs (p-value <0.001, odds ratio (95% confidence interval) = 4.15 (3.01-5.73)). Patients with simultaneous contact allergies to both linalool and limonene HPs had contact allergies to many other screening and fragrance allergens. CONCLUSIONS: Simultaneous positive PT reactions to allergens in baseline series and fragrances are common in patients with the HPs contact allergy, especially linalool HPs. The pattern of simultaneous PT reactions principally suggested the co-sensitization of the cosmetic allergens.

2-Cyanoethyl dimethyldithiocarbamate, a new contact allergen found in accelerator-free nitrile gloves.

BACKGROUND: Allergic contact dermatitis (ACD) from rubber glove usage is usually caused by rubber additives such as the accelerators. However, in analyses of the suspected gloves, ordinary rubber allergens are not always found. Accelerator-free rubber gloves are available, but some patients with accelerator allergy do not tolerate them and might also be patch test positive to them. OBJECTIVES: To identify and chemically characterize a new allergen, 2-cyanoethyl dimethyldithiocarbamate (CEDMC), in rubber gloves. We describe two patient cases: patient 1 that led us to the identification of CEDMC and patient 2 with occupational ACD caused by CEDMC. METHODS: The patients were examined with patch testing including baseline and rubber series, and their own rubber gloves. High-performance liquid chromatography (HPLC) was used for chemical analysis of rubber gloves. The allergen was synthesized and identified by nuclear magnetic resonance, mass spectrometry and infrared spectrometry, and tested on patient 2. RESULTS: CEDMC was identified by HPLC in a nitrile glove associated with hand eczema in patient 1. Patient 2 whose nitrile gloves contained CEDMC was patch test positive to CEDMC. CONCLUSIONS: CEDMC is a new contact allergen in nitrile gloves and probably forms during vulcanization from residual monomer acrylonitrile and rubber additives.

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.

Contact allergy investigations in healthcare workers with face mask-related skin disease.

BACKGROUND: During the COVID-19 pandemic, the use of face masks has increased among healthcare workers (HCWs). Questionnaire studies have shown a high frequency of self-reported facial adverse skin reactions. Case reports have been published on face mask-induced allergic contact dermatitis and urticaria. OBJECTIVES: To describe the results of the contact allergy investigations in consecutive HCWs investigated for skin reactions to face masks during the COVID-19 pandemic and the results of the chemical investigations of face masks supplied by the hospital. METHODS: Participants were patch tested with baseline series and chemicals previously reported in face masks not included in the baseline series. Face mask(s) brought by the HCW were tested as is and/or in acetone extract. Chemical analyses were performed on nine different face masks for potential allergens. RESULTS: Fifty-eight HCWs were investigated. No contact allergies were found to the face mask(s) tested. Eczema was the most common type of skin reaction, followed by an acneiform reaction. Colophonium-related substances were found in one respirator and 2,6-di-t-butyl-4-methylphenol (BHT) were found in two respirators. CONCLUSION: Based on this report, contact allergies to face masks is uncommon. Patch test with colophonium-related substances and BHT should be considered when investigating adverse skin reactions to face masks.

Active sensitization to dimethylthiocarbamylbenzothiazol sulphide: An unexpectedly strong rubber contact allergen.

BACKGROUND: The two dialkylthiocarbamyl benzothiazole sulphides, dimethyl-thiocarbamylbenzothiazole sulphide (DMTBS) and diethylthio-carbamylbenzothiazole sulphide (DETBS) were shown to be good markers of both thiuram and mercaptobenzothiazole sensitivity. OBJECTIVES: To investigate if DMTBS and/or DETBS could be better markers of contact allergy to common rubber additives than the ones currently used. METHODS: Sixty-eight dermatitis patients were patch tested with DMTBS and DETBS, both at 1% in petrolatum (pet). Because of late reactions in 10 patients, these were retested to DMTBS and DETBS in serial dilutions. Tetramethylthiuram monosulphide (TMTM) 1.0% pet was also tested. RESULTS: At the initial reading Days 3 and 7, no reactions were noted to DMTBS or DETBS. At retesting, 10 of the 68 (15%) patients reacted positively to lower concentrations of DMTBS than the initial test concentration. Seven of 8 also reacted to TMTM. Three of them had positive reactions to DEBTS. All 10 patients had reactions to more diluted solutions to DMBTS than to DEBTS (p = 0.0077; Mc-Nemar test, two-sided). CONCLUSIONS: Results speak for patch test sensitization to DMTBS with cross-reactivity to TMTM and also DEBTS. DMTBS and DEBTS could be new markers of rubber allergy but a safe test concentration must be found.

Gene profiling reveals a contact allergy signature in most positive Amerchol L-101 patch test reactions.

BACKGROUND: Diagnosis of contact allergy (CA) to Amerchol L-101 (AL-101), a marker for lanolin allergy, is problematic. Positive patch test reactions are frequently doubtful or weakly positive and difficult to associate with clinical relevance. OBJECTIVE: To gain further insight on the allergic or irritant nature of skin reactions induced by AL-101 patch test. METHODS: We re-tested in a dose-response fashion, 10 subjects with AL-101 CA and performed comprehensive transcriptomic analysis (gene arrays, quantitative real-time polymerase chain reaction [qRT-PCR]) of samples of their skin reactions. RESULTS: Eight of the 10 CA subjects reacted positively upon re-test, whereas two did not react. Most of AL-101 positive patch tests expressed an allergy signature with strong activation of gene modules associated with adaptive immunity and downregulation of cornification pathway genes. In addition, the breadth of gene modulation correlated with the magnitude of patch test reactions and the concentration of AL-101 applied. However, we observed that some of the positive patch test reactions to AL-101 expressed no/few allergy biomarkers, suggesting the induction of an irritant skin inflammation in these samples. CONCLUSIONS: This study confirms that AL-101 is an allergen that can cause both contact allergy and contact irritation. Our results also highlight that molecular profiling might help to strengthen clinical diagnosis.

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.

Skin Exposures, Hand Eczema and Facial Skin Disease in Healthcare Workers During the COVID-19 Pandemic: A Cross-sectional Study.

The COVID-19 pandemic has led to enhanced hygiene procedures and use of personal protective equipment, but also to increased attention to occupational skin disease in healthcare workers. The occurrence of hand and facial skin disease in > 5,000 Swedish healthcare workers was investigated in a questionnaire survey. Levels of skin exposure related to hygiene procedures and personal protective equipment were recorded. Caring for patients with COVID-19 entailed higher levels of wet work and face mask exposures, and was associated with higher 1-year prevalence of both hand eczema (36%) and facial skin disease (32%) compared with not being directly engaged in COVID-19 care (28% and 22%, respectively). Acne and eczema were the most common facial skin diseases; for both, a dose-dependent association with face mask use was found. Dose-dependent associations could be shown between hand eczema and exposure to soap and gloves, but not to alcohol-based hand disinfectants.

Skin exposure to the rubber accelerator diphenylguanidine in medical gloves-An experimental study.

BACKGROUND: Dermatitis caused by occupational contact allergy to rubber additives such as diphenylguanidine (DPG) in medical gloves is a hazard for healthcare workers. Both the duration of exposure to medical gloves and the number of gloves used per day vary. The use of alcoholic skin disinfectants before glove donning is mandatory. OBJECTIVES: To assess whether skin exposure to the rubber accelerator DPG released from glove material is influenced by alcoholic hand disinfectants, time, and pH. METHODS: With the use of ethanol washes, the amount of DPG left on the hands after wearing of gloves for 60 minutes was measured, and comparisons between hands exposed and not exposed to alcoholic disinfectant before glove donning were made. With the use of artificial sweat buffered at pH 4, 5, and 6, DPG release from the insides of gloves at different times was measured. RESULTS: The use of alcoholic disinfectant prior to polyisoprene glove donning increased the amount of DPG recovered from the hands. Of the DPG released from polyisoprene gloves into artificial sweat, almost 84% was released within 10 minutes. pH did not influence the rate of release. CONCLUSIONS: The use of alcoholic disinfectant increased skin exposure to the rubber accelerator DPG. Even a short duration of use of gloves results in substantial exposure to DPG.

The preservative 2-(thiocyanomethylthio)benzothiazole: A potential allergen in leather products.

BACKGROUND: Allergic contact dermatitis caused by leather is common, and several responsible allergens, such as tanning agents, glues, mercaptobenzothiazole derivatives, and dyes, but also antimicrobials and antifungals, are involved. MATERIAL AND METHODS: Three female patients were referred to the Departments of Dermatology in a Belgian university hospital following skin reactions caused by leather products (shoes, belt, and car seats). They were patch tested with the European baseline series and samples of suspected leather products, and additionally with 2-(thiocyanomethylthio)benzothiazole (TCMTB), an antifungal agent previously reported to be a contact allergen in footwear. Chromatographic analyses of samples of all the leather materials tested were performed at the Department of Occupational and Environmental Dermatology in Malmö, Sweden. RESULTS: The patients reacting to the leather samples were shown to be sensitized to TCMTB, the presence of which could be confirmed by chemical analyses of samples obtained from the patients. CONCLUSION: Patch tests with TCMTB should be considered in patients with contact dermatitis caused by leather items.

Hand eczema and occupational contact allergies in healthcare workers with a focus on rubber additives.

BACKGROUND: Hand eczema (HE) in healthcare workers (HCWs) is common. Besides wet work, healthcare work also implies exposure to contact allergens. OBJECTIVES: To assess HE and contact allergy related to occupational exposures in HCWs. METHODS: In a cross-sectional study, 311 HCWs with HE within the preceding 12 months and a control group of 114 HCWs without HE were investigated with the baseline series and a special patch test series based on substances found in the gloves, soaps, alcoholic hand disinfectants and hand creams provided at the hospitals. RESULTS: Contact allergy to rubber additives was significantly more common in HCWs with HE (6%) than in HCWs without HE (1%, P = .02). The corresponding percentages for fragrances were 11% and 3%, respectively (P = .004). Occupational HE was found in 193 of 311 (62%) HCWs. Of these, 22 of 193 (11%) had occupational allergic contact dermatitis, including 17 with glove-related rubber contact allergy. Contact allergy to diphenylguanidine was as common as contact allergy to thiurams. Occupational contact allergy to rubber additives was significantly associated with sick-leave related to HE. CONCLUSION: Contact allergy to rubber additives in medical gloves is the most common cause of occupational allergic contact dermatitis in HCWs. Aimed patch testing with relevant rubber additives is mandatory when HE in HCWs is investigated.

Allergic contact dermatitis caused by dimethylthiocarbamylbenzothiazole sulfide (DMTBS) in canvas shoes: in search of the culprit allergen.

BACKGROUND: During rubber vulcanization, new compounds can be formed. OBJECTIVES: To report a case of allergic shoe dermatitis in which the search for the allergen ultimately led to the identification of dimethylthiocarbamylbenzothiazole sulfide (DMTBS). METHODS: A female presented with eczema on her feet after wearing Sperry Top Sider® canvas sneakers. Patch testing was performed with the European baseline series, additional series, shoe materials, and extracts of shoe materials. Thin-layer chromatography (TLC) was performed for additional patch testing, and high-performance liquid chromatography and gas chromatography-mass spectometry were used for chemical analysis. RESULTS: Positive reactions were found to thiuram mix (+), tetramethylthiuram monosulfide (TMTM) (+), shoe material (+), and shoe extracts in eth. (++) and acetone (+). The extracts did not contain TMTM or other components of thiuram mix. TLC strips yielded a positive reaction (+) to one spot, whereas chemical analysis gave a negative result. Thereafter, a similar sneaker from another patient with shoe dermatitis was analysed, and DMBTS was identified. New extracts of the shoe of our first patient were then also shown to contain DMTBS. DMTBS as culprit allergen was confirmed by positive patch testing with a dilution series with DMTBS. CONCLUSION: DMBTS was identified as the culprit allergen in shoe dermatitis, giving rise to compound allergy. The positive reaction to TMTM was considered to represent cross-reactivity.

Contact dermatitis caused by a new rubber compound detected in canvas shoes.

BACKGROUND: In 2015 and 2016, female patients in Flanders consulted a dermatologist because they developed skin lesions after wearing a specific brand of canvas shoes. OBJECTIVES: To identify the culprit allergen in the shoes. METHODS: Eighteen young females aged 14-22 years presented with itching and erythematous to purple-coloured eczematous lesions on both feet. They were patch tested by 10 dermatologists with the European baseline series. Some patients underwent testing with additional series. Pieces of the shoe fabrics were tested in 11 of 18 patients. Chemical analysis of the shoe materials was performed. Finally, patients were tested with a thin-layer chromatogram of the shoe extracts and dilutions of the suspected rubber compound. RESULTS: All 18 patients showed positive reactions to thiuram mix. Ten of 11 patients reacted to a piece of shoe fabric. Chemical analysis showed the presence of dimethylthiocarbamylbenzothiazole sulfide (DMTBS). No thiurams were detected. Four patients tested with the chromatogram developed positive reactions to DMTBS. Positive reactions to low concentrations were observed in the 4 patients tested with a DMTBS dilution series; one patient reacted to 0.00001% in acetone. CONCLUSIONS: DMTBS, the culprit allergen, is a component formed during rubber vulcanization that probably cross-reacts with the thiuram mix.

Acetophenone azine: a new allergen responsible for severe contact dermatitis from shin pads.

BACKGROUND: Contact dermatitis resulting from the use of shin pads is usually caused by rubber components, dyes, benzoyl peroxide, or formaldehyde resins. OBJECTIVES: To investigate and identify a new allergen in shin pads that was responsible for severe contact dermatitis in a young football player. METHODS: High-performance liquid chromatography (HPLC) of samples of shin pads was performed. The boy was patch tested with pieces of shin pads and with acetophenone azine, a chemical substance identified by HPLC in the foam of the shin pads. RESULTS: HPLC identified acetophenone azine at concentrations of approximately 20 µg/g of shin pad samples. Patch tests gave strongly positive reactions to pieces of shin pads and to acetophenone azine down to 0.001% in acetone, whereas acetophenone and hydrazine sulfate were both negative. Twenty controls were negative for acetophenone azine 0.01% in acetone. CONCLUSIONS: Acetophenone azine is a new, strong allergen of shin pads, and more generally of other sport equipment based on ethylene vinyl acetate. It may be used as a biocide, but this has to be confirmed. Further investigations are needed to understand factors such as exposure, cross-reaction patterns, metabolism, and the optimal patch test preparation.

Reaction profile in patch testing with allergens formed during vulcanization of rubber.

BACKGROUND: Vulcanization of rubber changes its allergen pattern. OBJECTIVES: To estimate the contact allergic reactivity profile of users of finished rubber products. METHODS: Twenty-four patients with known contact allergy to rubber accelerators were patch tested with 21 compounds found in chemical analyses of vulcanized rubber products. No diphenylguanidine, p-phenylenediamine antioxidants or thioureas were included in the study. RESULTS: Thiuram monosulfides formed during vulcanization showed generally stronger test reactions than the corresponding thiuram disulfides. We also obtained more positive thiuram reactions to the monosulfides than to the disulfides. A positive reaction to a dithiocarbamate was accompanied by a positive reaction to the corresponding thiuram, except for 1 patient. The nitrogen substituents showed only minor differences between the methyl, ethyl and pentamethylene groups, but the butyl derivatives gave, in most cases, a negative response. Dialkylthiocarbamyl benzothiazole sulfides, formed between thiurams and mercaptobenzothiazoles during vulcanization, showed strong test reactions in almost all patients who were sensitive to dithiocarbamates, thiurams, or mercaptobenzothiazoles. CONCLUSIONS: We found thiuram monosulfides to be better markers of thiuram sensitivity than the corresponding disulfides or dithiocarbamates. Surprisingly, the dialkylthiocarbamyl benzothiazole sulfides were good markers of both thiuram and mercaptobenzothiazole sensitivity. This is an unexpected finding that needs to be confirmed in a larger study.