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Summary: Background: In contact dermatitis, it is crucial to understand and remember the outcome of patch testing. Unfortunately, many patients do not remember the results of their patch tests. Objectives: Our aim was to evaluate the effects of an intervention programme in which extensive information on specific contact allergy was provided, in individuals with positive patch test reactions. Methods: The study was designed as a randomized, investigator‐blinded clinical trial. Participants with positive test reactions were randomized into two groups that received either standard information according to clinical routine or standard information and a reminder letter. Knowledge of contact allergies was evaluated using questionnaires 12 months after inclusion. Results: There were 184 adults included in the trial and the response rate at 1‐year follow‐up was 78% (143 of 184). Sixty‐five per cent (45 of 69) in the intervention group and 54% (40 of 74) in the control group reported the correct name of the allergen (P = 0·23). Participants with several – as opposed to few – positive patch test reactions had difficulty in remembering the correct names of the allergens (P = 0·001). Moreover, the type of allergy had an influence on their ability to remember the name of the allergen correctly and their ability to make changes in lifestyle. Conclusions: The intervention performed did not significantly affect the participants' ability to remember their contact allergy. To achieve better knowledge and changes in lifestyle, efforts to inform should concentrate on individuals with several positive patch test reactions, those with particular allergens, individuals over 60 years of age, and – concerning changes in lifestyle – males. What is already known about this topic? Patch testing is crucial for patients with contact dermatitis.The ability to remember and understand the outcome of the patch testing is fundamental.Unfortunately, many patients do not remember or have misunderstood the results of their patch tests. Patients who require more information should be identified. What does this study add? This study suggests that participants' ability to remember and understand their patch test results, and also to make changes in lifestyle, are dependent on factors such as the number of contact allergies, which allergy they have, age and sex.The results highlight the importance of making further efforts to gain higher efficacy in the information and education given. It is therefore valuable to take special care with these patients and to cautiously educate and inform them about the results of patch tests. Linked Comment:Korkmaz and Boyvat. Br J Dermatol 2021; 184:2. Plain language summary available online [ABSTRACT FROM AUTHOR]

At evaluation of contact dermatitis caused by solid material, patch testing is usually performed with the material as such and with extracts of it. In this study, optimization of the extraction technique monitored by quantitative HPLC analysis of the extracted haptens is described for mercaptobenzothiazole derivatives. Several solvents with different properties are included. Acetone has traditionally been a solvent widely used for the extraction of organic haptens from solid products. However, acetone and other ketones are not inert solvents. The rubber accelerators 2-(4-morpholinyl mercapto) benzothiazole (MMBT) and N-cyclohexyl-2-benzothiazyl sulfenamide (CBS) react with acetone, yielding 2 new compounds. which were isolated and characterised by NMR and MS. For the extraction of solid rubber products, methyl tert-butyl ether (MTBE) was found to be a more suitable solvent which is unreactive to most common haptens. [ABSTRACT FROM AUTHOR]

Background: Rubber gloves contain rubber accelerators that may cause contact allergy. The content of sensitising rubber accelerators in contemporary rubber gloves is not well known., Objectives: Identify and quantify the content of rubber accelerators in disposable rubber gloves., Methods: Fifty-one gloves of 49 different brands were collected. Forty-eight of the gloves were disposable and three re-usable. The gloves were analysed for their content of sensitising rubber accelerators, that is, zinc dithiocarbamates, thiurams, thiazoles/benzothiazoles, diphenylguanidine, and thioureas by high-performance liquid chromatography., Results: Rubber accelerators were identified in 43/48 (90%) of the disposable gloves. In total, 39 gloves contained zinc dibutyldithiocarbamate (ZDBC) (0.18-1.96 mg/g), 34 zinc diethyldithiocarbamate (ZDEC) (0.032-2.78 mg/g), three zinc dibenzyldithiocarbamate (0.65-1.4 mg/g), one zinc dimethyldithiocarbamate (0.23 mg/g), and one 1,3-diphenylguanidine (0.21 mg/g). 2-cyanoethyl dimethyldithiocarbamate (CEDMC) was identified in three gloves (<0.052 mg/g). The one glove labelled as accelerator free contained ZDBC (1.07 mg/g). Only few glove packages had the specific content of rubber accelerators labelled., Conclusions: The most frequent rubber accelerators in rubber gloves are ZDEC and ZDBC. Accelerator-free gloves may contain rubber accelerators. Full labelling of rubber gloves is needed and producers should be sure not to falsely claim that the rubber gloves are free of rubber accelerators., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Rubber accelerators are used in the vulcanization of rubber. However, rubber accelerators for example tetraethylthiuram disulfide (TETD) and zinc diethyldithiocarbamate (ZDEC) may cause contact allergy. Concomitant reactions between ZDEC and TETD have been observed in patients which could be explained by co- or cross-reactivity., Objectives: To investigate cross-reactivity between TETD and ZDEC and vice versa., Methods: Groups of mice were sensitized with TETD or ZDEC based on reported EC3-values. Proliferation of lymphocytes were measured on day 5. To test cross-reactivity, mice were sensitized and challenged 3 weeks later with TETD or ZDEC. The inflammatory response was measured by changes in ear thickness and the proliferative response in CD4 + and CD8 + T cells in the submandibular and cervical draining lymph nodes., Results: Sensitization of mice with doses of ZDEC 3%, TETD 5.6% or TETD 16.2% induced significant increased ear thickness and proliferation of CD4 + and CD8 + T cells. Challenge with ZDEC or TETD in these groups induced significant increased ear thickness. Challenge with ZDEC in mice sensitized to TETD 5.6% or TETD 16.2% induced significant increased proliferation of CD4 + and CD8 + T cells., Conclusions: We show cross-reactivity between TETD and ZDEC. Patients sensitized to TETD or ZDEC should avoid exposure to both ZDEC and TETD., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: Allergic contact dermatitis (ACD) from protective gloves is often caused by rubber additives, such as accelerators. However, while accelerator-free rubber gloves are available, they still cause ACD in some individuals., Objectives: A new allergen, 2-cyаnоethyl dimethyldithiocarbamate, (CEDMC), has recently been identified in accelerator-free gloves, and we here provide a first in vitro characterisation of CEDMC in a dendritic cell (DC)-like cell model along with three reference sensitizer rubber chemicals, consisting of tetraethylthiuram disulfide (TETD) and two xanthogenates., Methods: Cellular responses after the exposure to the rubber chemicals were assessed using a transcriptomic approach, multiplex cytokine secretion profiling, and flow cytometry to determine DC model activation marker expression and apoptosis induction., Results: CEDMC and all other sensitizers were classified as strong skin sensitizers with the transcriptomic approach. They all significantly increased IL-8 secretion and exposure to all except one increased CD86 DC activation marker expression. When tested, CEDMC induced apoptosis, however, delayed compared to TETD., Conclusions: The in vitro data corroborate CEDMC, TETD, and investigated xanthogenates as skin sensitizers. Transcriptomic analyses further reveal unique cellular responses induced by CEDMC, which together with future study can contribute to better understanding of cellular mechanisms underlying the sensitising capacity of rubber chemicals., (© 2024 The Author(s). Contact Dermatitis published by John Wiley & Sons Ltd.)

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., (© 2024 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

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., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2021 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Background: A patient received enoxaparin sodium subcutaneous injections for prophylaxis after surgery and developed inflammatory skin reactions on injection sites on Day 5 after the first administration. Patch test was performed with baseline series and low-molecular-weight heparins (LMWHs) at different concentrations and showed positive reactions to neomycin and LMWHs. Cross-reactivity between neomycin and LMWHs was suspected due to similar structure., Objectives: To establish the evidence of possible cross reaction between neomycin and LMWHs by patch testing., Materials & Methods: Patch testing of 12 individual controls with a history of neomycin contact allergy was performed., Results: Positive patch test reactions to enoxaparin sodium, tinzaparin sodium, and neomycin sulphate were reported in the patients. None of the controls reacted to LMWHs., Conclusion: There was no proof of cross reaction between neomycin and LMWHs in this study, suggesting that the simultaneous reaction may be a coincidence. Since the number of individuals studied was low, allergy to LMWHs following injection in individuals with a history of neomycin allergy should be further investigated.

Allergic contact dermatitis (ACD) is one of the most common forms of immunotoxicity, and increased understanding of how chemicals trigger these adverse reactions is needed in order to treat or design testing strategies to identify and subsequently avoid exposure to such substances. In this study, we investigated the cellular response induced by rubber chemicals in a dendritic cell (DC) model, focusing on the structurally similar chemicals diethylthiocarbamylbenzothiazole sulfide and dimethylthiocarbamylbenzothiazole sulfide, with regard to regulation of microRNA, and messenger RNA expression. Only a few miRNAs were found to be commonly regulated by both rubber chemicals, among them miR1973, while the overall miRNA expression profiles were diverse. Similarly, out of approximately 500 differentially regulated transcripts for each chemical, about 60% overlapped, while remaining were unique. The pathways predicted to be enriched in the cell model by stimulation with the rubber chemicals were linked to immunological events, relevant in the context of ACD. These results suggest that small structural differences can trigger specific activation of the immune system in response to chemicals. The here presented mechanistic data can be valuable in explaining the immunotoxicological events in DC activation after exposure to skin sensitizing chemicals, and can contribute to understanding, preventing and treating ACD., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Acetophenone azine (AA) has recently been identified as a new allergen in shin pads and sports shoes. We report the case of a boy with allergic contact dermatitis of the shins caused by AA present in his shin pads. High-performance liquid chromatography of samples of shin pads was performed to help identify potential contact allergens. Patch tests revealed strongly positive reactions to pieces of his shin pads and to AA down to a concentration of 0.001% in acetone. To our knowledge, this is the first reported case of allergic contact dermatitis to AA in the United Kingdom. Here we recommend the optimal concentration of AA for patch testing at 0.1% in acetone and summarize previous relevant published cases.

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., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)