Wet work and hand eczema in apprentice nurses; part I of a prospective cohort study.

BACKGROUND /OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. Here, we report an investigation on wet work exposure and its influence on the risk of developing hand eczema in apprentice nurses. METHODS: A prospective cohort study was performed among 721 Dutch apprentice nurses. Participants recorded wet work exposure and symptoms of hand eczema using specially designed diary cards. RESULTS: For 533 apprentice nurses, a follow-up time of 1-3 years was completed. Diary cards were supplied by 383 students. The 1-year period prevalence of hand eczema was 23% in the first year, 25% in the second year and 31% in the third year of follow-up. Eighty-one new cases of hand eczema developed, most of which occurred during the first year of follow-up. In approximately one-third of the participants, wet work exposure exceeded the national guidelines. Frequent hand washing during traineeships [odds ratio (OR) 1.5; 90% confidence interval (CI) 1.0-2.3], frequent hand washing at home (OR 2.3; 90% CI 1.5-3.7) and having a side job involving wet work (OR 1.6; 90% CI 1.0-2.4) were independent risk factors for hand eczema. CONCLUSION: As a considerable number of apprentice nurses had already developed hand eczema during traineeships, more attention should be paid to skin protection in vocational education.

Filaggrin loss-of-function mutations and atopic dermatitis as risk factors for hand eczema in apprentice nurses: part II of a prospective cohort study.

BACKGROUND/OBJECTIVES: Environmental exposure and personal susceptibility both contribute to the development of hand eczema. In this study, we investigated the effect of loss-of-function mutations in the filaggrin gene (FLG), atopic dermatitis and wet work exposure on the development of hand eczema in apprentice nurses. METHODS: Dutch apprentice nurses were genotyped for the four most common FLG mutations; atopic dermatitis and hand eczema history were assessed by questionnaire. Exposure and hand eczema during traineeships were assessed with diary cards. RESULTS: The prevalence of hand eczema during traineeships was higher among subjects with a history of hand eczema reported at inclusion. Hand washing during traineeships and at home increased the risk of hand eczema. After adjustment for the effects of exposure and FLG mutations, an odds ratio of 2.5 (90% confidence interval 1.7-3.7) was found for a history of atopic dermatitis. In this study, an increased risk of hand eczema conferred by FLG mutations could not be shown, but subjects with concomitant FLG mutations and atopic dermatitis showed the highest risk of hand eczema during traineeships. CONCLUSION: A history of atopic dermatitis, a history of hand eczema and wet work exposure were the most important factors increasing the risk of hand eczema during traineeships.

Quantification of wet-work exposure in nurses using a newly developed wet-work exposure monitor.

Occupational contact dermatitis (OCD) is an important work-related disease. A major cause of OCD is 'wet work': frequent contact of the skin with water, soap, detergents, or occlusive gloves. The German guidance TRGS 401 recommends that the duration of wet work (including use of occlusive gloves) should not exceed 2 h day(-1) and also the frequency of hand washing or hand disinfection should be taken into account. This highlights the need for a reliable method to assess duration and frequency of wet work. Recently, a wet-work sampler has been developed by the University of Aberdeen. The sampler uses the temperature difference (ΔT) generated by evaporative cooling between two sensors: one sensor on the skin and a second one placed 2 mm above the skin. We have evaluated the use of this sampler in a healthcare setting, using direct observation as reference. Twenty-six nurses wore the sampler on the volar side of the middle finger for ∼2 h during their regular daily tasks, while being observed by a researcher. Sampler results were evaluated using various threshold values for ΔT to identify wet events of the hands. The optimal ΔT to discern wet and dry skin differed considerably between individual nurses. Individual results yielded a median sensitivity of 78 and 62% and a median specificity of 79 and 68% for indicating wet skin and glove use, respectively. Overall, the sampler was moderately accurate for identifying wetness of the skin and less accurate for discerning glove use. In conclusion, agreement between observed wet work and device-reported wet events in healthcare settings was not high and further adaptations and developments may be required.

Polymorphisms in the interleukin-1 gene influence the stratum corneum interleukin-1 alpha concentration in uninvolved skin of patients with chronic irritant contact dermatitis.

BACKGROUND: Interleukin (IL)-1 alpha and its receptor antagonist IL-1 ra play a role in skin inflammation. Several polymorphisms in the IL1 gene cluster, coding for IL-1 alpha, IL-1 ra, and IL-1 beta, influence their protein expression. Within this cluster, strong linkage disequilibrium has been shown. OBJECTIVE: We studied the association between the polymorphisms IL1A-889 (C-->T) and IL1B-31 (T-->C) and the concentration of IL-1 alpha and IL-1 ra in the stratum corneum (SC). METHOD: In 124 patients with chronic irritant contact dermatitis, we genotyped the IL1A-889 and IL1B-31 polymorphisms and determined the amount of IL-1 alpha and IL-1 ra on tape strips obtained from uninvolved skin of the volar forearm. RESULTS: The SC IL-1 alpha concentration was 23% and 47% lower in subjects with IL1A-889 C/T genotype and T/T genotype, respectively, compared with wild-type genotype. In subjects with IL1B-31 C/C genotype, the IL-1 alpha concentration was 51% lower compared with C/T and T/T genotypes. The ratio IL-1 ra/IL-1 alpha increased twofold in IL1A-889 C/T genotype and threefold in T/T genotype compared with wild type. CONCLUSIONS: We have shown a clear effect of IL1 genotype on protein expression in the SC. This altered expression may be responsible for the interindividual differences in the inflammatory response of the skin.

Cytokine gene polymorphisms and susceptibility to chronic irritant contact dermatitis.

BACKGROUND: Cytokines play an important role in skin inflammation. OBJECTIVES: We determined whether polymorphisms in cytokine genes contribute to the occurrence of occupational chronic irritant contact dermatitis (CICD). METHODS: In a case-control study, 9 polymorphisms in the genes coding for interleukin (IL)-1 alpha, IL-1 beta, IL-8, IL-10, and tumour necrosis factor (TNF)-alpha were determined in 197 patients with CICD. 217 apprentices in vocational training for high-risk occupations for CICD served as controls. RESULTS: For all polymorphisms, no differences in genotype distributions were found between patients and controls. However, in patients with self-reported low levels of wet work and irritant exposure, more TNFA -308 variant genotypes (G/A and A/A) were present compared with those exposed to higher levels or controls, which indicates a TNFA-induced increase of susceptibility. In patients with TNFA -308 variant genotypes, the prevalence of flexural eczema was higher (48% and 57%) compared with that in patients presented with wild-type genotype (30%). Regarding IL1A -889, prevalence of symptoms of dermatitis was lower in apprentices with T/T or C/T genotype (32% and 36%) compared with wild-type genotype (54%, C/C). This indicates a protective effect of these variant alleles in acquiring hand dermatitis. CONCLUSIONS: This study provides evidence that some genetic variations alter susceptibility to (chronic) dermatitis. Knowledge of the impact of genetic differences on the risk of CICD is essential in predictive testing of individuals at risk.

Percutaneous absorption of m-xylene vapour in volunteers during pre-steady and steady state.

Percutaneous absorption of m-xylene (XYL) was determined in volunteers exposed to 29.4 microg cm(-3) XYL vapour on the forearm and hand for 20, 45, 120 and 180 min. The internal exposure was assessed by measuring the concentration of XYL in exhaled air. The systemic kinetics were determined using a reference exposure by inhalation. The dermal permeation rate and the cumulative absorption of XYL as a function of time were calculated using mathematical deconvolution. From these relationships, the average flux into the skin throughout the exposure (J(skin, average)) and the maximal flux into the blood (J(blood, max)) were derived. Both fluxes were dependent on the duration of exposure, approaching each other at longer exposure durations. The values of J(skin, average), adjusted to a concentration of 1 microg cm(-3), were 0.091 microg cm(-2) h(-1) during 20-min exposure falling to 0.072, 0.066 and 0.061 microg cm(-2) h(-1) for 45, 120 and 180 min, respectively. The values of J(blood, max) showed an opposite trend, gradually increasing from 0.034 microg cm(-2) h(-1) at an exposure duration of 20 min to 0.042, 0.059 and 0.063 microg cm(-2) h(-1) for 45, 120 and 180 min of exposure durations, respectively.

Revealing barriers and facilitators to use a new genetic test: comparison of three user involvement methods.

We compared three common user involvement methods in revealing barriers and facilitators from intended users that might influence their use of a new genetic test. The study was part of the development of a new genetic test on the susceptibility to hand eczema for nurses. Eighty student nurses participated in five focus groups (n = 33), 15 interviews (n = 15) or questionnaires (n = 32). For each method, data were collected until saturation. We compared the mean number of items and relevant remarks that could influence the use of the genetic test obtained per method, divided by the number of participants in that method. Thematic content analysis was performed using MAXQDA software. The focus groups revealed 30 unique items compared to 29 in the interviews and 21 in the questionnaires. The interviews produced more items and relevant remarks per participant (1.9 and 8.4 pp) than focus groups (0.9 and 4.8 pp) or questionnaires (0.7 and 2.3 pp). All three involvement methods revealed relevant barriers and facilitators to use a new genetic test. Focus groups and interviews revealed substantially more items than questionnaires. Furthermore, this study suggests a preference for the use of interviews because the number of items per participant was higher than for focus groups and questionnaires. This conclusion may be valid for other genetic tests as well.

Chronic solvent-induced encephalopathy: European consensus of neuropsychological characteristics, assessment, and guidelines for diagnostics.

INTRODUCTION: The presence of neuropsychological impairment is a hallmark of chronic solvent-induced encephalopathy (CSE), and using clinical neuropsychological procedures to generate a valid assessment of the condition is crucial for its diagnosis. The goals of this consensus document are to provide updated knowledge of the neuropsychological characteristics of CSE and to provide internationally acceptable guidelines for using neuropsychological assessments in the process of diagnosing patients who are suspected of having CSE. MATERIALS AND METHODS: A European working group that was composed of experts in the field of the clinical diagnosis of CSE met at several round-table meetings and prepared this report. The first section of the consensus paper addresses a review of the relevant literature that was published between 1985 and March 2012. The second section addresses recommendations for the clinical neuropsychological assessment of patients who are suspected of having CSE. RESULTS: The literature review indicates that the most common neuropsychological impairments in CSE patients are within the domains of attention, particularly the speed of information processing, memory, and motor performance. It appears that the influence of CSE on memory processes mainly involves immediate recall and generally involves verbal, visual and visuospatial material. In the second section, six recommendations are presented regarding important functional domains for the neuropsychological diagnostic process of CSE that relate to the evaluation of neuropsychological impairment, the assessment and evaluation of symptoms, differential diagnostic considerations, the reliability and validity of neuropsychological test results, and the retesting of patients. DISCUSSION AND CONCLUSIONS: These recommendations will contribute to the improvement of the process for accurately diagnosing CSE, better counselling for CSE patients, the comparability of epidemiological data between countries, and finally, by raising awareness, these recommendations will contribute to combating the adverse health effects of occupational exposure to solvents.

Decision rules for assessment of chronic solvent-induced encephalopathy: Results in 2370 patients.

For the diagnosis of patients suspected of chronic solvent-induced encephalopathy (CSE), it would be helpful if the applied cognitive tests show a characteristic profile of impairment in this disease. We investigated the existence of such a profile. In 1997-2006 two expert teams in The Netherlands systematically examined 2370 patients referred for evaluation of suspected CSE. The procedure included two selection steps: (1) intake interview, using criteria of exposure, development of symptoms and absence of non-solvent causes, and (2) seven tests of the computerized Neurobehavioural Evaluation System (NES). Patients showing negligible impairments were considered free from CSE and were not further examined. The third step comprised a neuropsychological, neurological and exposure evaluation. Explicit decision rules for the diagnosis of CSE were developed, including a minimum score for cognitive impairment summarizing 25 cognitive tests. These rules were retroactively applied to 563 patients, comprising 513 patients who had regularly completed all diagnostic steps and a sample of 50 out of the approximately 450 patients with negligible impairments on the NES, who were fully examined. The data from this sample were extrapolated to the original number of 450. In the combined population of 963 patients, a calculated 301 patients were given the diagnosis 'Solely CSE', 242 'CSE and other disease', 158 'Other Disease' and 262 'No (known) disease'. In the Solely CSE patients, the most impaired tests regarded Verbal Fluency & -Similarities, Motor Speed and Simple Attention. A profile of test results that might support the identification of patients with CSE amongst the other referred patients, was not found. The diverging results of related cognitive tests indicate that the use of a core test battery is needed to improve comparability. We consider the decision rules as a step towards a more objective assessment of CSE.

Individual susceptibility to occupational contact dermatitis.

Occupational Contact Dermatitis (OCD) is one of the most common work-related diseases. High risk occupations are in health care, hairdressing, food sector and metal industry. OCD tends to become chronic; persistent OCD often results in impaired quality of life and loss of work ability. The purpose of this article is to review the present knowledge on the factors which determine individual susceptibility to acquire OCD. Recent discoveries regarding genes involved in the skin barrier, inflammatory response and biotransformation of xenobiotics provide more insight in the individual susceptibility for OCD. Knowledge of the factors which predispose to OCD is useful in occupational health practice for the application of preventive measures and for career guidance for apprentices and workers in high risk occupations.

Altered penetration of polyethylene glycols into uninvolved skin of atopic dermatitis patients.

Involved regions of the skin in atopic dermatitis (AD) patients have an altered barrier function. Whether uninvolved skin also has a diminished barrier is controversial. To assess the barrier function of uninvolved skin in AD patients, the percutaneous penetration of polyethylene glycols (PEGs) of various molecular sizes was determined in vivo in AD patients and control subjects using tape stripping of the stratum corneum (SC). The diffusion and partition coefficients were determined using Fick's second law of diffusion. The SC thickness was similar in both groups; however, the trans-epidermal water loss was higher in atopic skin. The apparent diffusion coefficient of PEGs through atopic skin was twice as high as through normal skin, and decreased with increasing molecular weight (MW) in both groups. The partition coefficient in the skin of AD patients was half of that for normal skin but as for normal skin, there was no MW dependency. Although atopic skin exhibited altered barrier with respect to diffusion and partitioning, the permeability coefficients were nearly the same for atopic and normal skin. The results support the assumption of altered skin barrier of AD patients even in the skin that is visibly unaffected by disease.

Differential cytokine expression in skin after single and repeated irritation by sodium lauryl sulphate.

In vivo levels of cytokines and presence of neutrophils and eosinophils in skin irritation are not well known. Our objective was to get more insight in inflammatory mediators and markers involved in single and repeated skin irritation. We sampled epidermis-derived fluid using a novel technology that includes application of a negative pressure on the skin after creation of micropores in the stratum corneum by a laser. In nine volunteers, transdermal fluid was sampled after a single 4-h 10% sodium lauryl sulphate exposure and a repeated 3-week exposure (0.1% sodium lauryl sulphate). Twenty-seven cytokines were assessed by multiplex assay, and IL-1alpha, eosinophil cationic protein and myeloperoxidase by enzyme-linked immunosorbent assay. Levels of eosinophil cationic protein were increased after irritation and correlated with levels of myeloperoxidase. The levels of inflammatory mediators showed large interindividual differences in unexposed and exposed skin. Despite this variation, several mediators clearly showed increased levels: CC chemokine ligand (CCL)11, CXCL10 and vascular endothelial growth factor after both single and repeated exposure, IL-1alpha and basic fibroblast growth factor after single exposure and interleukin-1 receptor antagonist (IL-1RA) after repeated exposure. After repeated exposure, CCL5 and the ratio IL-1RA/IL-1alpha both increased compared with single exposure. We conclude that single and repeated irritation induces differential and concerted expression of various inflammatory mediators and markers.

Cytokines at different stratum corneum levels in normal and sodium lauryl sulphate-irritated skin.

BACKGROUND/PURPOSE: Cytokines play an important role in inflammatory and repair processes occurring in the skin. The objectives of this study were to determine the amounts of cytokines and protein isolated by tape stripping in the different layers of the stratum corneum (SC), and to compare normal skin with skin exposed in vivo to the irritant sodium lauryl sulphate (SLS). METHODS: In eight volunteers, we determined the amount of total and soluble protein and also interleukin-1alpha (IL-1alpha) in pooled tape strips obtained from the upper, intermediate and lower parts of the SC. Three different types of tape were compared (Diamond , D-squame or Sentega tape). In a separate study, 20 volunteers were repeatedly exposed to 0.1% SLS over a 3-week period. The amounts of IL-1alpha, IL-1RA and IL-8 in strips obtained from the three different SC levels of SLS-exposed skin were compared with an unexposed site. RESULTS: For normal skin, the amounts of soluble protein and IL-1alpha were similar for the three tapes. Diamond tape showed the highest yield of total protein. The total protein yield per strip decreased to lower SC levels, whereas soluble protein and IL-1alpha normalized by soluble protein did not change across the SC. After SLS induced skin irritation, IL-1alpha decreased and IL-1RA and IL-8 increased at increasing depth into the SC. CONCLUSIONS: Tape stripping is a suitable method to determine SC cytokine concentrations in human skin. With this technique, it is possible to study changes in cytokine concentrations at different SC layers after skin irritation.

Genetic polymorphism of metabolic enzymes modifies the risk of chronic solvent-induced encephalopathy.

In the present study, we investigate whether genetic polymorphism in enzymes involved in the metabolism of organic solvents influences susceptibility to chronic solvent encephalopathy (CSE), which is one of the major effects of long-term exposure to organic solvents. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1 enzymes were determined in a group of male CSE patients (N=97) and controls (N=214). The selection of the patients was based on a standard diagnostic protocol, including interviews, neuropsychological tests and questionnaires directed to somatic, cognitive and mood symptoms and exposure, in combination with well-defined decision rules. As controls, healthy workers of similar socio-economic background, without memory problems and with no known exposure to organic solvents, were included in the study. Comparing patients and controls, higher frequencies of the variant *5B allele of the CYP2E1 gene (OR: 5.8; 95% CI: 1.8-18.8) and of the variant GSTP1*C allele (OR: 0.40; 95% CI: 0.17-0.94) were found. Homozygous carriers of the exon 4 EPHX1 Arg139 variant allele had a lower risk (OR: 0.25; 95% CI: 0.06-1.13). The present study indicates that genetic polymorphism of CYP2E1, EPHX1 and GSTP1 modify the risk of developing CSE.

Increased permeability for polyethylene glycols through skin compromised by sodium lauryl sulphate.

In this in vivo human study we assessed the influence of skin damage by sodium lauryl sulphate (SLS) on percutaneous penetration of polyethylene glycols (PEGs) of different molecular weights (MW). Percutaneous penetration of PEGs was determined using tape stripping of the stratum corneum (SC). The forearm skin of volunteers was pretreated with 5% w/w SLS for 4 h, and 24 h later patches with PEGs were applied for 6 h. The penetration parameters were deduced by data regression to Fick's law for unsteady-state diffusion. The trans-epidermal water loss (TEWL) increased after SLS treatment from 6.3 +/- 2.1 to 17.9 +/- 8.7 g/m(2)/h. The diffusion coefficient for all PEGs was increased in the SLS-damaged skin. The increase was smaller for higher MW. In addition, the partition coefficient of PEGs between SC and water was larger in the SLS-compromised skin and showed a tendency to increase with MW. The permeability coefficient decreased gradually with increasing MW of PEGs in both control and SLS-compromised skin. SLS caused a threefold increase in the permeability coefficient for all MWs ranging in control skin from 0.34 to 0.70 x 10(-5) cm/h and in the SLS-compromised skin from 1.20 to 2.09 x 10(-5) cm/h for MW of 590-282 Da. The results of this study show the deleterious effect of SLS on the skin barrier for hydrophilic PEGs. A defective skin barrier will facilitate absorption of other chemicals and local skin effects.

Stratum corneum cytokines and skin irritation response to sodium lauryl sulfate.

Little is known about cytokines involved in chronic irritant contact dermatitis. Individual cytokine profiles might explain at least part of the differences in the individual response to irritation. Our objective was to investigate the relation between baseline stratum corneum (SC) cytokine levels and the skin response to a single and a repeated irritation test. This study also aimed to determine changes in SC cytokine levels after repeated irritation. Transepidermal water loss (TEWL) and erythema were measured in 20 volunteers after single 24-hr exposure to 1% sodium lauryl sulfate (SLS), and during and after repeated exposure to 0.1% SLS over a 3-week period. SC cytokine levels were measured from an unexposed skin site and from the repeatedly exposed site. Interleukin (IL)-1alpha decreased by 30% after repeated exposure, while IL-1RA increased 10-fold and IL-8 increased fourfold. Baseline IL-1RA and IL-8 values were predictors of TEWL and erythema after single exposure (r = 0.55-0.61). 6 subjects showed barrier recovery during repeated exposure. Baseline IL-1RA and IL-8 levels are likely to be indicators of higher skin irritability after single exposure to SLS. Barrier repair in some of the subjects might explain the lack of agreement between the TEWL response after single and repeated irritation.

Visual evoked potentials in workers with chronic solvent encephalopathy.

OBJECTIVES: Two promising variations of visual evoked potentials (VEPs) were studied in solvent-exposed workers: the effect of a low-contrast stimulus in comparison with the usually applied high contrast, and the ability of pattern-onset VEP to reveal damage to specific visual cortical areas. In addition, we studied disturbances of a visual event-related potential (P300). METHODS: Thirty male patients (48 +/- 9 years of age) with solvent-induced chronic encephalopathy, and 41 controls (46 +/- 8 years) without solvent exposure, participated. Pattern-reversal checkerboards with low (11%) contrast and with high (93%) contrast between the checks were used. For onset VEPs two dedicated stimulus patterns were used. P300 was elicited with an "oddball" paradigm. RESULTS: At low contrast the N75-P100 peak-to-peak amplitude in the controls was 9.6 +/- 4.9 microV, i.e. 57% of the amplitude at high contrast (16.3 +/- 7.2 microV). In the patients the response at low contrast was only 48% of that at high contrast; the corresponding amplitudes were 7.5 +/- 3.5 microV and 15.8+/-4.9 microV. For the pattern-onset VEPs no effect of exposure was found. With regard to the P300, the patients missed more targets (average 3.6%) than did the controls (average 0.5%). Patients had a smaller P300 amplitude (8.8 +/- 4.5 microV) than the controls (11.5 +/- 5.3 microV), and a longer latency (390 +/- 34 ms compared to 376 +/- 24 ms). CONCLUSION: The results point to a physiological basis for the solvent-induced decrease of visual contrast sensitivity as found by others by means of psychophysical methods. The results also suggest that the neurophysiological examination of the visual system in persons who have undergone exposure to toxins might be benefited by the addition of low-contrast stimuli.