An Analysis of Skin Prick Tests to Latex and Patch Tests to Rubber Additives and other Causative Factors among Dental Professionals and Students with Contact Dermatoses.

BACKGROUND: Dental workers often experience unwanted allergic and nonallergic skin reactions resulting in different contact dermatoses (e.g., contact urticaria, irritant and allergic contact dermatitis) that are often attributed to rubber gloves. OBJECTIVE: To examine allergic and nonallergic contact dermatoses by different methods amongst dental professionals and dental students, more specifically, reactions to natural rubber latex (NRL), rubber additives, and other causative factors. METHODS: In this cross-sectional study we surveyed a total of 444 subjects (dentists, assistants, technicians, and students); 200 agreed to be tested to latex by the standard skin prick test (SPT) and prick-by-prick test, of whom 107 were patch tested to rubber additives (mercapto mix, thiuram mix, carba mix, and N-isopropyl-N-phenyl-4-phenylenediamine [IPPD]). RESULTS: Skin lesions appeared significantly more frequently with longer work experience (p = 0.002; V = 0.181), frequent glove changes (p < 0.001; V = 0.310), and hand washing (p < 0.001; V = 0.263), and in subjects with a history of allergies (atopic dermatitis, allergic rhinitis, allergic conjunctivitis, and others) (p < 0.001; V = 0.183). Positive SPTs to latex occurred in 14/200 subjects (7%), of whom 5/14 subjects (35.7%) were also positive in prick-by-prick tests. Patch tests were positive in 5/104 subjects (4.8%) (mercapto mix 1%, thiuram mix 1.9%, and carba mix 1.9%). CONCLUSION: Only a small number of our subjects were allergic to latex (7%) or rubber additives (4.8%). Thus, self-reported contact dermatoses (during NRL product use) in dental professionals and students are not commonly caused by allergies to latex and rubber additives, as is often assumed, but by other factors.

Occupational contact sensitization in female geriatric nurses: Data of the Information Network of Departments of Dermatology (IVDK) 2005-2014.

BACKGROUND: Geriatric nurses (GN) have a high risk of occupational contact dermatitis (OCD), with chronic irritant contact dermatitis predominating. However, allergic contact dermatitis is an important issue as well. Little is known whether the relevant occupational allergen spectrum reported in the 1990s, including fragrances, preservatives, rubber chemicals and ingredients of surface disinfectants to be the most common sensitizers in GN, is still valid. OBJECTIVES: To monitor the current allergen spectrum in GN with OCD and verify the validity of the patch test recommendations (baseline-, preservative-, ointment base-, rubber-, disinfectant, series and fragrances) in GN with suspected OCD given by the German Contact Dermatitis Research Group (DKG). METHODS: Retrospective analysis of IVDK data (2005-2014) of 743 female GN with OCD, in comparison to 695 GN without OCD. RESULTS: GN with OCD reacted significantly more frequently to both fragrance mixes, hydroxyisohexyl 3-cyclohexene carboxaldehyde (HICC), thiuram mix, zinc diethyldithiocarbamate and mercaptobenzothiazole than GN without OCD. Reactions to MDBGN, methylchloroisothiazolinone/methylisothiazolinone and oil of turpentine occurred substantially, but not significantly more frequently among GN with OCD. The latter may be due to former use of a special alcoholic liniment in geriatric care. Among material from the patients' workplaces, tetrazepam was a frequent allergen, due to dust exposure from pill crushing. Furthermore, occupationally used protective gloves, body care products as well as surface disinfectants were often tested positively. CONCLUSIONS: The general allergen spectrum in GN with OCD is unchanged, so the DKG patch test recommendations are still valid. Prevention of occupational sensitization should focus on fragrance-free hygiene and body care products, usage of accelerator-free protective gloves and avoidance of drug dust exposure.

Rubber: new allergens and preventive measures.

Natural rubber latex (NRL) and rubber accelerators are well-known causes of occupational skin diseases. The latest epidemiological data on rubber allergy show that rubber additives are still among the allergens most strongly associated with occupational contact dermatitis, however, a decrease in NRL allergy has been confirmed. A review of recent publications on rubber allergens based on the Pubmed database is presented. New glove manufacturing processes have been developed, such as low-protein natural rubber gloves, vulcanisation accelerator-free gloves, or specific-purpose gloves containing antimicrobial agents or moisturisers. Several websites provide information on allergens found in gloves and/or glove choice according to occupation.

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.

[Clinical epidemiology and prevention of contact allergies. The Information Network of Departments of Dermatology (IVDK) as a register and surveillance system]. / Klinische Epidemiologie und Prävention der Kontaktallergien. Der Beitrag des Informationsverbundes Dermatologischer Kliniken (IVDK).

A total of 56 departments of dermatology from Germany, Austria, and Switzerland collaborate to study the clinical epidemiology of contact allergies (CA). Data generated in the course of the diagnostic work-up of CA (e.g., patch test data) have been stored since 1989 in the data center in Göttingen, Germany, including data for more than 200,000 patients (March 2011). These data can be used as a register and as a surveillance system. Analysis of the register may identify and quantify risk factors of sensitization to an allergen, which is exemplified with the case of the allergen para-phenylenediamine. It turned out that-in addition to the risk factor hair dyeing-other important risk factors must be considered. In contrast, data collected every 6 months (from approximately 6,000 patients) allow for time-trend analyses of allergens, thus, identifying allergens of concern, which is of utmost importance for early preventive intervention. Here, the epidemiology of allergies to epoxy resins serves as an example. Continuous monitoring of contact allergens will also be mandatory in the future, as the CA premarketing screening systems will have imperfect predictive values with regard to human CA risk. Unfortunately, the (current) national regulatory framework severely hampers clinical surveillance/epidemiology of contact sensitization and, thus, prevention of contact allergy.

Positive patch test reactions in older individuals: retrospective analysis from the North American Contact Dermatitis Group, 1994-2008.

BACKGROUND: Relatively little is known about the epidemiology of allergic contact dermatitis in older individuals. OBJECTIVES: We sought to determine the frequency of positive and clinically relevant patch test reactions in older individuals (≥ 65 years old) referred for patch testing, and to compare these results with those of adults (≤ 64-19 years) and children (<18 years). DESIGN: This was a retrospective cross-sectional analysis of North American Contact Dermatitis Group data from 1994 to 2008. RESULTS: A total of 31,942 patients (older n = 5306; adults n = 25,028; children n = 1608) were patch tested. The overall frequency of at least one allergic reaction in older individuals was 67.3% as compared with 66.9% for adults (P = .5938) and 47% for children (P = .0011). Reaction rates that were statistically higher in older individuals as compared with both adults and children included: Myroxylon pereirae, fragrance mix I, quaternium-15, formaldehyde, imidazolidinyl urea, diazolidinyl urea, neomycin, bacitracin, methyldibromo glutaronitrile, methyldibromo glutaronitrile/phenoxyethanol, ethyleneurea melamine formaldehyde mix, and carba mix (P values < .0004). Patch test reaction rates that were significantly lower in older individuals than both comparison groups included: nickel, thimerosal, and cobalt (P values < .0001). LIMITATIONS: Referral population was a limitation. CONCLUSIONS: Older individuals were more likely to have at least one positive patch test reaction as compared with children, but had similar rates to adults. The frequency of positive reactions to specific allergens differed by age group, most likely as a result of exposures.

Contact allergy to thiurams: multifactorial analysis of clinical surveillance data collected by the IVDK network.

PURPOSE: To analyse the association between occupation (represented by job title) and contact allergy to thiuram vulcanising agents based on data of a clinical registry (IVDK, www.ivdk.org ). METHODS: Clinical, demographic and allergy patch test data of all patients tested between 1992 and 2006 with the thiuram mix (1% in petrolatum) as part of the baseline series was analysed (n = 121,051). Poisson regression analysis was used to quantify the association between different occupations (and other relevant factors) and a positive patch test reaction to the thiuram mix. Furthermore, the time trend of sensitisation prevalence was analysed in high-risk occupational subgroups identified. RESULTS: In comparison to a largely unexposed reference group (office workers and teachers), rubber manufacturers had a significantly elevated risk (prevalence ratio (PR): 5.1, 95% confidence interval (CI) 2.0-10.5). However, health care workers such as physicians and dentists (PR: 3.8, 95% CI: 3.0-4.8) or nursing staff (PR: 3.0, 95% CI: 2.5-3.6) as well as meat and fish processors (PR 3.5, 95% CI: 2.2-5.3) and cleaners (PR 3.1, 95% CI: 2.5-3.8) were found to have a high sensitisation risk as well. In case of health care workers, a significant downward trend during the study period was observed; while in food processors and cleaners, sensitisation prevalence remained largely stable. CONCLUSION: The adjusted multifactorial analysis identified occupations yet unknown to be associated with elevated thiuram contact allergy risk, e.g., food processors and cleaners. Thus, (i) further in-depth research can be targeted and (ii) efforts to prevent sensitisation to thiurams focussed, e.g., by limiting thiuram concentrations in products to a residual level which is technically inevitable.

Thiuram allergy--a potential dermal allergy among health care workers.

Occupational health nurses should be cognizant of the myriad exposures that can result in dermal reactions among health care workers.

Patch testing discordance alert: false-negative findings with rubber additives and fragrances.

From July 1996 through June 1998, the North American Contact Dermatitis Group evaluated 318 patients for suspected contact dermatitis by patch testing simultaneously with Finn Chambers and the T.R.U.E. Test allergen system. Discrepancies between the two systems were found in some of the results, particularly with fragrance and rubber allergens. These results suggest that positive reactions to fragrance, thiuram, and carba mix allergens may be missed if the T.R.U.E. Test is used alone.

Development of an immunoassay (ELISA) for the quantification of thiram in lettuce.

Two competitive immunoassays, a laboratory assay based on microwell plates and a field test based on the use of polystyrene tubes, have been developed for the quantification of thiram in lettuces. Concerning the laboratory assay, the calibration curve for thiram had a linear range of 11 to 90 ng/mL and a detection limit of 5 ng/mL. Precision of the assay presented coefficient of variation values <9% and the recovery of thiram from lettuce averaged 89% across the range of the immunoassay method using 30 min extraction with water/acetone (50:50, v/v). The tube-based method was developed in order that an extract of lettuce, containing thiram at the MRL (8 ppm), would be found on the linear part of the standard curve. The calibration curve for thiram has a linear range of 100 to 800 ng/mL (1.39 to 11.1 ppm in lettuce) and a detection limit of 40 ng/mL.

A quantitative method for assessing the sensitizing potency of low molecular weight chemicals using a local lymph node assay: employment of a regression method that includes determination of the uncertainty margins.

Risk assessment of sensitizing chemicals requires, besides hazard identification, the assessment of potency. To examine the sensitizing capacity of low molecular weight chemicals, a murine local lymph node assay (LLNA) was used. The sensitizing capacity of known allergens was quantified by dose-response modeling. At a stimulatory index (SI) of 3, the corresponding estimated concentration was calculated (EC(3)), together with a confidence interval to take account of the quality of the particular data set. We tested ten allergens (ethyl-p-aminobenzoate (benzocaine), diethylamine (DEA), 2,4-dinitrochlorobenzene (DNCB), 2-mercaptobenzothiazole (MBT), 4-ethoxymethylene 2-phenyl oxazol-5-one (oxazolone), phthalic anhydride (PA), toluene diisocyanate (TDI), trimellitic anhydride (TMA), tetramethylthiuramdisulfide (TMTD) and zincdimethyldithiocarbamate (ZDMC)). Oxazolone showed the strongest sensitizing potency followed in this order by DNCB, TDI, TMA, PA, TMTD, ZDMC, MBT, benzocaine and DEA. The approach performed in this study is a way to accurately assess the potency of sensitizing chemicals and thus a possibility for classification.

Contact sensitivity to chromate: comparison at a London contact dermatitis clinic over a 10-year period.

It has been argued that for chromate sensitivity to be reduced, then ferrous sulfate should be added to cement. This has not yet been done in the UK. To explore this further, we have looked at the comparative sensitization rates of patients attending the St. John's Institute of Dermatology Contact Dermatitis Clinic between the years 1982-3 and 1992-3. Patch-test-positive rates for females were not significantly different between the 2 populations studied (1982-3, 1.59% and 1992-3, 1.99% p NS). Similarly, there was no significantly different rate between the males (1982-3, 3.99% and 1992-3, 4.25% p NS) in the same time period. There was no difference in the distribution of eczema in chromate-positive subjects, nor of cobalt co-sensitization, a crude indicator of sensitization via cement. This work demonstrates no appreciable difference in the frequency of chromate sensitivity between the early 1980s and 1990s in London. Adding ferrous sulfate to cement may help to lower the frequency in the future.

Contact allergy and exposure patterns to thiurams and carbamates in consecutive patients.

Sensitization to rubber is most often due to sensitization to thiurams. Positive patch test reactions to carbamates are less frequent, and usually only diagnosed in patients with positive patch test reactions to thiurams as well. The aim of the present study was to describe the relative frequency of sensitization to thiuram mix (TH mix) and zinc diethyldithiocarbamate (ZDC) in a population where the exposure to these chemicals from rubber gloves was previously studied and considered to be of approximately the same order of magnitude. The thiuram derivatives seemed to be the most important sensitized (frequency 2.8%) compared to ZDC (frequency 0.5%), which has been the most frequently reported sensitizer among the carbamates in rubber gloves. An interesting observation was that the probability that the patient was reacting to ZDC was strongly associated with the strength of the patch test reaction to TH mix. This observation may add a new aspect to the discussion about cross-reactivity versus concomitant sensitization of thiurams and carbamates.

Release of thiurams and carbamates from rubber gloves.

A method for quantitative determination of thiuram and carbamate derivatives released from rubber gloves into synthetic sweat is presented. The analysis was based upon determination of ester derivatives using gas-chromatography/mass spectrometry and isotope-dilution. The detection limit was 0.1 mg thiuram/carbamate in 200 ml synthetic sweat (0.5 ppm). The release of thiurams and carbamates from 5 household and 5 surgical types of gloves into synthetic sweat was determined. Each of the natural rubber gloves released varying amounts of thiurams (0-4.3 mg) as well as carbamates (0-8.1 mg). 22 thiuram-sensitized patients were patch tested with pieces of the gloves. Gloves releasing considerable amounts of thiurams and/or carbamates seemed to cause more positive patch test reactions in these patients than gloves releasing smaller amounts. Surgical gloves made from natural rubber caused a substantial larger number of positive patch test reactions than household gloves made from natural rubber. The amounts released per cm2 of the gloves were of the same order of magnitude as the content per cm2 patch test of thiuram mix, diluted 1:10. The accessibility of a quantitative, chemical analysis for thiurams and carbamates released from rubber gloves makes it reasonable to ask for declarations of rubber gloves. Proposals for threshold values for release of thiurams and carbamates from rubber gloves may be given in the future.

Evaluation of contact sensitivity of rubber chemicals using the murine local lymph node assay.

The sensitizing abilities of 4 rubber additives, tetramethylthiuram disulfide (TMTD). 2-mercaptobenzothiazole (MBT), N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD) and zinc diethyldithiocarbamate (ZDEC), were evaluated using the murine local lymph node assay. Exposure to IPPD induced a significant increase of lymph node cell proliferation in the draining lymph nodes even at a low concentration. Exposure to TMTD and MBT induced moderate proliferative responses, while ZDEC induced a weak proliferation even at the higher concentrations. The sensitizing potency of each chemical was described in terms of the concentration that increased lymph node cell proliferation by a factor of 2 over that in the vehicle-treated control group. The concentrations of IPPD, TMTD, MBT and ZDEC were 0.14%, 0.35%, 4.2% and > 10%, respectively.

The problem of the sensitization to dithiocarbamates in thiuram-allergic patients.

Because of the occurrence of hand dermatitis in members of a surgical staff due to allergy to thiuram-containing rubber gloves, an investigation was performed about cross-sensitization between thiuram compounds and dithiocarbamates. Positive reactions to dithiocarbamates were compared with reactions to 8 brands of hypo-allergenic or dithiocarbamate-containing surgical gloves. There appeared to be a marked difference in reactions to the dithiocarbamate-containing gloves. Some brands gave negative or nearly always negative reactions, while other brands caused many positive reactions. Thiuram-allergic patients were advised to wear nonreacting rubber gloves or PVC gloves.