Assessment of cytotoxicity and sensitization potential of intradermally injected tattoo inks in reconstructed human skin.

BACKGROUND: The number of people within the European population having at least one tattoo has increased notably, and with it the number of tattoo-associated clinical complications. Despite this, safety information and testing regarding tattoo inks remain limited. OBJECTIVE: To assess cytotoxicity and sensitization potential of 16 tattoo inks after intradermal injection into reconstructed human skin (RHS). METHODS: Commercially available tattoo inks were injected intradermally into RHS (reconstructed epidermis on a fibroblast-populated collagen hydrogel) using a permanent makeup device. RHS biopsies, tissue sections, and culture medium were assessed for cytotoxicity (thiazolyl blue tetrazolium bromide assay [MTT assay]), detrimental histological changes (haematoxylin and eosin staining), and the presence of inflammatory and sensitization cytokines (interleukin [IL]-1α, IL-8, IL-18; enzyme-linked immunosorbent assay). RESULTS: Varying degrees of reduced metabolic activity and histopathological cytotoxic effects were observed in RHS after ink injection. Five inks showed significantly reduced metabolic activity and enhanced sensitization potential compared with negative controls. DISCUSSION: Using the RHS model system, four tattoo inks were identified as highly cytotoxic and classified as potential sensitizers, suggesting that allergic contact dermatitis could emerge in individuals carrying these inks. These results indicate that an RHS-based assessment of cytotoxicity and sensitization potential by intradermal tattoo ink injection is a useful analytical tool to determine ink-induced deleterious effects.

Updating exposure assessment for skin sensitization quantitative risk assessment for fragrance materials.

In 2008, a proposal for assessing the risk of induction of skin sensitization to fragrance materials Quantitative Risk Assessment 1 (QRA1) was published. This was implemented for setting maximum limits for fragrance materials in consumer products. However, there was no formal validation or empirical verification after implementation. Additionally, concerns remained that QRA1 did not incorporate aggregate exposure from multiple product use and included assumptions, e.g. safety assessment factors (SAFs), that had not been critically reviewed. Accordingly, a review was undertaken, including detailed re-evaluation of each SAF together with development of an approach for estimating aggregate exposure of the skin to a potential fragrance allergen. This revision of QRA1, termed QRA2, provides an improved method for establishing safe levels for sensitizing fragrance materials in multiple products to limit the risk of induction of contact allergy. The use of alternative non-animal methods is not within the scope of this paper. Ultimately, only longitudinal clinical studies can verify the utility of QRA2 as a tool for the prevention of contact allergy to fragrance materials.

Evaluating the effect of electronic monitoring and feedback on hand cream use in healthcare workers: Healthy Hands Project.

BACKGROUND: Healthcare workers (HCWs) are at high risk of developing hand dermatitis (HD). Current guidelines on HD prevention recommend the use of emollients; however, in practice, adherence is poor. OBJECTIVE: To assess whether the provision of creams, electronic monitoring and feedback on cream consumption can improve skin care in HCWs. METHODS: A cluster randomized controlled trial was conducted on 19 academic hospital wards, including 501 HCWs, for 12 months. The intervention wards (n = 9; 285 HCWs) were provided with hand cream dispensers equipped with an electronic system to monitor use, which was regularly communicated to the HCWs by the use of posters. The process outcomes were self-reported cream consumption in both groups, and electronically measured consumption per ward in the intervention group (IG) vs the control group (CG). RESULTS: Self-reported cream use at follow-up was significantly higher in the IG than in the CG, before (odds ratio [OR] 2.27; 95%CI: 1.29-3.97; P = 0.004) and during (OR 3.30; 95%CI: 1.80-6.06, P < 0.001) the shift, whereas at baseline there was no difference between the groups. In the IG, electronically measured cream use was, on average, 0.4 events per shift per HCW. CONCLUSION: The intervention improved hand cream use, and may therefore be considered as a practical strategy to promote skin care in HCWs. Notwithstanding this, the application frequency remained lower than recommended in the present study and current guidelines.

Assessment of metal sensitizer potency with the reconstructed human epidermis IL-18 assay.

According to the new EU Medical Devices (MDR) legislation coming into effect in 2017, manufactures will have to comply with higher standards of quality and safety for medical devices in order to meet common safety concerns regarding such products. Metal alloys are extensively used in dentistry and medicine (e.g. orthopedic surgery and cardiology) even though clinical experience suggests that many metals are sensitizers. The aim of this study was to further test the applicability domain of the in vitro reconstructed human epidermis (RhE) IL-18 assay developed to identify contact allergens and in doing so: i) determine whether different metal salts, representing leachables from metal alloys used in medical devices, could be correctly labelled and classified; and ii) assess the ability of different salts for the same metal to penetrate the skin stratum corneum. Twenty eight chemicals including 15 metal salts were topically exposed to RhE. Nickel, chrome, gold, palladium were each tested in two different salt forms, and titanium in 4 different salt forms. Metal salts were labelled (YES/NO) as sensitizer if a threshold of more than 5 fold IL18 release was reached. The in vitro estimation of expected sensitization induction level (potency) was assessed by interpolating in vitro EC50 and IL-18 SI2 with LLNA EC3 and human NOEL values from standard reference curves generated using DNCB (extreme) and benzocaine (weak). Metal salts, in contrast to other chemical sensitizers and with the exception of potassium dichromate (VI) and cobalt (II) chloride, were not identified as contact allergens since they only induced a small or no increase in IL-18 production. This finding was not related to a lack of stratum corneum skin penetration since EC50 values (decrease in metabolic activity; MTT assay) were obtained after topical RhE exposure to 8 of the 15 metal salts. For nickel, gold and palladium salts, differences in EC50 values between two salts for the same metal could not be attributed to differences in molarity or valency. For chrome salts the difference in EC50 values may be explained by different valencies (VI vs. III), but not by molarity. In general, metal salts were classified as weaker sensitizers than was indicated from in vivo LLNA EC3 and NOEL data. Our in vitro results show that metals are problematic chemicals to test, in line with the limited number of standardized human and animal studies, which are not currently considered adequate to predict systemic hypersensitivity or autoimmunity, and despite clinical experience, which clearly shows that many metals are indeed a risk to human health.

Contact dermatitis is an unrecognized problem in the construction industry: Comparison of four different assessment methods.

BACKGROUND: A high contact dermatitis symptoms prevalence has been observed in Dutch construction workers. METHODS: Contact dermatitis was diagnosed by an expert panel using questionnaire data and photographs of 751 subjects' hands. A subset was evaluated by two occupational physicians. Their diagnoses were compared to those of the expert panel. In addition, two self-reported questionnaire-based assessment methods were compared to the expert panel evaluation. Associations between contact dermatitis and determinants were assessed using log-binomial regression analysis. RESULTS: Contact dermatitis prevalence was high: 61.4% (expert panel's diagnosis) and 32.9% (self-reported). Agreement between occupational physicians and the expert panel was low but increased after training. Washing hands with solvents and performing job-related tasks at home were related to contact dermatitis. CONCLUSIONS: Contact dermatitis prevalence among construction workers is high. Recognition of contact dermatitis by occupational physicians is poor but can be improved by training. Awareness of skin disorders should be raised.

Economic evaluation of an integrated care programme for patients with hand dermatitis.

BACKGROUND: Hand dermatitis has a large impact on society as a whole. OBJECTIVES: To evaluate the cost-effectiveness of integrated, multidisciplinary care as compared with usual care (UC) for patients with moderate to severe chronic hand dermatitis after 52 weeks. METHODS: Patients (n = 196) visiting the dermatology department at one of the participating hospitals for hand dermatitis were randomized to integrated care (IC) or UC. IC was provided by a multidisciplinary team, and integrated clinical and occupational care to optimize treatment of hand dermatitis. Effect outcomes were clinical assessment of hand dermatitis with the Hand Eczema Severity Index (HECSI), and disease-specific quality of life, work performance and quality-adjusted life-years with the EQ-5D. Incremental cost-effectiveness ratios (ICERs) were calculated. The ICER indicates the additional investment needed to gain one unit of effect. RESULTS: The HECSI difference between both groups after 52 weeks was 8.7 (standard error 5.3, 95% confidence interval -1.8-18.9). No differences were found on secondary outcome measures. Mean total costs with IC (€ 3613; SD 798) were significantly higher than with UC (€ 1576, SD 430). The ICER for improvement in HECSI score was -247. IC was not considered to be cost-effective as compared with UC. The probability that IC was cost-effective was 90% at a ceiling ratio of € 1500 per additional point improvement in HECSI score. CONCLUSION: Integrated care was neither cost-effective, nor effective after 12 months follow-up, in contrast to our findings after 6 months. Decision makers should decide whether the clinical benefits of integrated care on the short term outweigh the higher costs compared to usual care.

Hands4U: a multifaceted strategy to implement guideline-based recommendations to prevent hand eczema in health care workers: design of a randomised controlled trial and (cost) effectiveness evaluation.

BACKGROUND: Workers in wet work occupations have a risk for developing hand eczema. Prevention strategies exist, but compliance to the proposed recommendations is poor. Therefore, a multifaceted implementation strategy (MIS) is developed to implement these recommendations to reduce hand eczema among health care workers performing wet work. METHODS/DESIGN: This study is a randomised controlled trial in three university hospitals in the Netherlands. Randomisation to the control or intervention group is performed at department level. The control group receives a leaflet containing the recommendations only. The intervention group receives the MIS which consists of five parts: 1) within a department, a participatory working group is formed to identify problems with the implementation of the recommendations, to find solutions for it and implement these solutions; 2) role models will help their colleagues in performing the desired behaviour; 3) education to all workers will enhance knowledge about (the prevention of) hand eczema; 4) reminders will be placed at the department reminding workers to use the recommendations; 5) workers receive the same leaflet as the control group containing the recommendations. Data are collected by questionnaires at baseline and after 3, 6, 9 and 12 months. The primary outcome measure is self-reported hand eczema. The most important secondary outcome measures are symptoms of hand eczema; actual use of the recommendations; sick leave; work productivity; and health care costs.Analyses will be performed according to the intention to treat principle. Cost-effectiveness of the MIS will be evaluated from both the societal and the employer's perspective. DISCUSSION: The prevention of hand eczema is important for the hospital environment. If the MIS has proven to be effective, a major improvement in the health of health care workers can be obtained. Results are expected in 2014. TRIAL REGISTRATION NUMBER: NTR2812.

Assessment of contact allergen cross-reactivity by retesting.

At former allergic contact dermatitis reaction sites retesting causes augmented hyper-reactivity, characterized by an accelerated onset within a few hours. This expression of 'local skin memory' has been ascribed to locally persisting allergen-specific effector/memory T cells. To verify this hypothesis, we investigated whether accelerated retest reactivity also occurs with cross-reactive allergens. Guinea pigs were immunized with either or both 2,4-dinitrochlorobenzene (DNCB) and 2-hydroxyethyl methacrylate (HEMA), and primary skin tests to these and cross-reactive methacrylic compounds were performed 12-21 days later. Subsequently, new skin tests were conducted 3 weeks later both at the former test ('retest') and contralateral, non-pretreated test ('control') sites, and skin test readings started 2 h later. Retest reactivity was evaluated by comparing retest and contralateral control reactions. Both contact sensitizers, HEMA and DNCB, induced strong retest reactivity, peaking at 4-6 h. Fully allergen-specific retest reactivity was observed when primary skin tests had been postponed until 21 days after immunization, most probably reflecting loss of accumulation of irrelevant allergen-primed T cells at that time. As hypothesized, retesting with various methacrylate congeners at primary HEMA, but not DNCB, skin test sites showed early hyperreactivity strengths in line with those observed earlier in conventional cross-reactivity studies. These results, therefore, support the view that local skin memory exhibits allergen specificity through residual allergen-primed T cells. Because the retesting procedure is readily applicable in clinical practice, it provides a tool not only for confirmation of doubtful contact allergic skin reactions, but also for distinguishing between true cross-reactivity and coincident multiple sensitization in man.