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.

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.

Allergic contact dermatitis and other occupational skin diseases in health care workers in the Finnish Register of Occupational Diseases in 2005-2016.

BACKGROUND: Health care workers are an important risk group for occupational skin disease (OSD). AIMS: To study diagnoses and causes of OSDs in health care workers in the Finnish Register of Occupational Diseases (FROD) in 2005-2016. METHODS: We searched the FROD for dermatological cases (a) in health care-related occupations defined by ISCO-08 and (b) in the industrial branch of health care defined by European industry standard classification system (NACE rev. 2). RESULTS: Health care workers comprised 19% of all OSD cases in the FROD, and irritant contact dermatitis dominated the diagnoses. Nurses and assistant nurses were the largest occupational groups with incidence rates of 3.3 and 2.7/10 000 person years, respectively. Rubber chemicals were by far the most common causative agents of allergic contact dermatitis (ACD) followed by preservatives, the latter mainly comprising isothiazolinones and formaldehyde. Acrylates were important allergens in dental professions. Metals and coconut fatty acid derivatives were the next largest causative groups for ACD. Drugs caused only 1% of the ACD cases. CONCLUSIONS: Workers in different health care occupations do not have a uniform risk for OSD, but they share the risk for ACD due to rubber chemicals and various preservatives.

Occupational allergic contact dermatitis: A 24-year, retrospective cohort study from Turkey.

BACKGROUND: Limited data exist on occupational allergic contact dermatitis (OACD) in Turkey. OBJECTIVES: To investigate the epidemiologic profile of OACD in Turkey. METHODS: A retrospective cohort study on 294 patients with OACD among 2801 consecutively patch-tested patients in the Allergy Unit of the Dermatology Department of Istanbul Faculty of Medicine between 1996 and 2019. RESULTS: The overall prevalence of OACD was 10.5%, showing a male predominance. OACD was most frequently seen in construction workers (45.2%), followed by hairdressers, metalworkers, health care workers, and miscellaneous. The main relevant allergens were chromium in cement, thiurams in rubber gloves, hairdressing chemicals, resins/glues/plastics, metals, isothiazolinones, and fragrances. Hands were the mainly involved site (95.6%). Airborne eczema was observed in 21.4%. Hand and foot eczema and co-sensitizations to chrome and thiuram and chrome and cobalt were significantly associated with being a construction worker. Sensitizations to isothiazolinones in house painters, ammonium persulfate and p-phenylenediamine in hairdressers, and colophonium increased after 2010. CONCLUSION: This was the largest group of data on OACD from Turkey, reflecting the importance of rubber glove allergy in all occupations and the striking increase in ammonium persulfate allergy among hairdressers. Chrome and cobalt were still the main cement allergens in Turkey, where the cement directive is not yet in force.

Relevance of contact sensitizations in occupational dermatitis patients with special focus on patch testing of workplace materials.

BACKGROUND: Studies on patch testing with workplace materials and evaluation of current occupational relevance of positive patch test reactions are scarce in patients with occupational dermatitis (OD). OBJECTIVES: To identify frequent sensitizations with occupational relevance and to determine the value of patch testing with workplace materials in OD patients. PATIENTS AND METHODS: Results and clinical data of 654 patients with suspected OD patch tested between 2013 and 2017 were analysed. RESULTS: Occupational allergic contact dermatitis was diagnosed in 113 (17.3%) patients. Mechanics had the widest range of occupational sensitizations. Sensitization to epoxy resin was rated occupationally relevant in almost all handicraft trades. Among positive patch test reactions to workplace products, those to water-based metal working fluids and leave-on cosmetic products were most frequent. Despite frequent testing, protective gloves only rarely elicited positive reactions. Preservatives and rubber compounds were most frequently identified as currently occupationally relevant. CONCLUSIONS: Rubber allergy is occupationally relevant especially in healthcare workers and cleaners. Generally, preservatives including formaldehyde releasers are important allergens in OD patients. Leave-on cosmetic products must not be forgotten as allergen sources. Patch testing both workplace materials and standardized test preparations has a complementary value and is beneficial for the diagnostic work-up of OD patients.

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.

Patch test results with rubber series in the European Surveillance System on Contact Allergies (ESSCA), 2013/14.

BACKGROUND: Contact allergy to rubber additives is common, particularly in patients with occupational dermatitis. OBJECTIVES: To descriptively analyse and compare patch test reactions in patients patch tested both with the baseline series and with an additional 'rubber series' as used in the department. METHODS: Patch test data from those members of the European Surveillance System on Contact Allergies (ESSCA) network (www.essca-dc.org) who also contributed data on rubber series patch test results were retrospectively analysed. RESULTS: Among 29 522 patients patch tested, 2870 were eligible, that is, patch tested both with the baseline series and with a special rubber series. Of these, 8.8% had positive reaction(s) to one of the baseline screening rubber allergens (as compared with 4.2% in all patients), most often to carba mix, 12.3% had positive reaction(s) to allergens from an additional rubber series, and 6.4% had positive reaction(s) to both. CONCLUSIONS: Additional testing with a dedicated rubber series, containing break-down single ingredients of mixes from the baseline series and additional rubber allergens, is warranted in patients with suspected contact allergy to rubber, to avoid false-negative results.

Occupational skin disease among Australian healthcare workers: a retrospective analysis from an occupational dermatology clinic, 1993-2014.

BACKGROUND: Healthcare workers (HCWs) are at risk of developing occupational skin disease (OSD). OBJECTIVES: To ascertain the causes of OSD in Australian HCWs in a tertiary referral clinic. METHODS: A retrospective review was performed of patients assessed at the Occupational Dermatology Clinic in Melbourne from 1993 to 2014. RESULTS: Of 685 HCWs assessed in the clinic over a period of 22 years, 555 (81.0%) were diagnosed with OSD. The most common diagnosis was irritant contact dermatitis (ICD) (79.1%), followed by allergic contact dermatitis (ACD) (49.7%). Natural rubber latex allergy was also relatively frequent (13.0%). The major substances causing ACD were rubber glove chemicals (thiuram mix and tetraethylthiuram disulfide), preservatives (formaldehyde, formaldehyde releasers, and isothiazolinones), excipients in hand cleansers, which are hard-to-avoid weak allergens, and antiseptics. ACD caused by commercial hand cleansers occurred more frequently than ACD caused by alcohol-based hand rubs (ABHRs). Occupational ICD was mostly caused by water/wet work and hand cleansers, and environmental irritants such as heat and sweating. CONCLUSIONS: Understanding the causes of OSD in HCWs is important in order to develop strategies for prevention. We suggest that skin care advice should be incorporated into hand hygiene education. The use of ABHRs should be encouraged, weak allergens in skin cleansers should be substituted, and accelerator-free gloves should be recommended for HCWs with OSD.

Investigation of diethylthiourea and ethyl isothiocyanate as potent skin allergens in chloroprene rubber.

BACKGROUND: Exposure to chloroprene rubber has resulted in numerous cases of allergic contact dermatitis, attributed to organic thiourea compounds used as vulcanization accelerators. However, thiourea compounds are not considered to be strong haptens. OBJECTIVES: To analyse common commercial chloroprene materials for their contents of diethylthiourea (DETU), dibutylthiourea (DBTU), diphenylthiourea (DPTU), and their degradation products, isothiocyanates; and to investigate the sensitization potencies of possible degradation products of the mentioned thiourea compounds. METHODS: Liquid chromatography/mass spectrometry (MS) was used for quantification of organic thiourea compounds in chloroprene products, such as medical, sports and diving gear; isothiocyanates were measured by solid-phase microextraction/gas chromatography/MS. Sensitization potencies were determined with the murine local lymph node assay (LLNA). RESULTS: DETU was identified at concentrations of 2.7-9.4 µg/cm(2) in all samples, whereas neither DBTU nor DPTU was detected. At 37°C, degradation of DETU in the materials to ethyl isothiocyanate (EITC) was detected. EITC and ethyl isocyanate showed extreme and strong sensitization potencies, respectively, in the LLNA. CONCLUSIONS: DETU can act as a prehapten, being degraded to EITC when subjected to body temperature upon skin contact. EITC could thus be the culprit behind allergic contact dermatitis caused by chloroprene rubber.