Basal cell carcinoma risk and solar UV exposure in occupationally relevant anatomic sites: do histological subtype, tumor localization and Fitzpatrick phototype play a role? A population-based case-control study.

BACKGROUND: A two-fold risk increase to develop basal cell carcinoma was seen in outdoor workers exposed to high solar UV radiation compared to controls. However, there is an ongoing discussion whether histopathological subtype, tumor localization and Fitzpatrick phototype may influence the risk estimates. OBJECTIVES: To evaluate the influence of histological subtype, tumor localization and Fitzpatrick phototype on the risk to develop basal cell carcinoma in highly UV-exposed cases and controls compared to those with moderate or low solar UV exposure. METHODS: Six hundred forty-three participants suffering from incident basal cell carcinoma in commonly sun-exposed anatomic sites (capillitium, face, lip, neck, dorsum of the hands, forearms outside, décolleté) of a population-based, case-control, multicenter study performed from 2013 to 2015 in Germany were matched to controls without skin cancer. Multivariate logistic regression analysis was conducted stratified for histological subtype, phototype 1/2 and 3/4. Dose-response curves adjusted for age, age2, sex, phototype and non-occupational UV exposure were calculated. RESULTS: Participants with high versus no (OR 2.08; 95% CI 1.24-3.50; p = 0.006) or versus moderate (OR 2.05; 95% CI 1.15-3.65; p = 0.015) occupational UV exposure showed a more than two-fold significantly increased risk to develop BCC in commonly UV-exposed body sites. Multivariate regression analysis did not show an influence of phototype or histological subtype on risk estimates. The restriction of the analysis to BCC cases in commonly sun-exposed body sites did not influence the risk estimates. The occupational UV dosage leading to a 2-fold increased basal cell carcinoma risk was 6126 standard erythema doses. CONCLUSION: The risk to develop basal cell carcinoma in highly occupationally UV-exposed skin was doubled consistently, independent of histological subtype, tumor localization and Fitzpatrick phototype.

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population-based case-control study FB-181.

BACKGROUND: Squamous cell carcinoma (SCC) is one of the most frequent types of cancer constituting a significant public health burden. Prevention strategies focus on limiting ultraviolet (UV) exposure during leisure time. However, the relative impact of occupational and nonoccupational UV exposure for SCC occurrence is unclear. OBJECTIVES: To investigate the association between occupational and nonoccupational UV exposure for SCC in a multicentre population-based case-control study hypothesizing that high occupational UV exposure increases the risk of SCC. METHODS: Consecutive patients with incident SCC (n = 632) were recruited from a German national dermatology network. Population-based controls (n = 996) without history of skin cancer were recruited from corresponding residents' registration offices and propensity score matched to cases. Lifetime UV exposure, sociodemographic and clinical characteristics were assessed by trained physicians. Occupational and nonoccupational UV exposure doses were estimated by masked investigators using established reference values. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were assessed using conditional logistic regression adjusting for relevant confounders. RESULTS: Total solar UV exposure was significantly associated with increased SCC. The OR for high (> 90th percentile) vs. low (< 40th percentile) and high vs, moderate (40-59th percentile) occupational UV exposure was 1·95 (95% CI 1·19-3·18) and 2·44 (95% CI 1·47-4·06) for SCC. Adjusting for occupational UV exposure, nonoccupational UV exposure was not significantly related to SCC incidence. Dose-response relationships were observed for occupational but not for nonoccupational solar UV exposure. CONCLUSIONS: Solar occupational UV exposure is a major determinant of incident SCC. Our findings indicate that prevention strategies should be further expanded to the occupational setting.

[Skin and occupational artificial UV-radiation]. / Haut und berufliche UV-Strahlung künstlicher Quellen.

In various areas of professional activity, exposure of skin to ultraviolet radiation coming from artificial sources may occur. These UV rays differ from the solar UV radiation due to their intensity and spectrum. We review current developments with the introduction of statutory exposure limit values for jobs with UV radiation from artificial sources, a selection of relevant activities with artificial UV exposure and an overview of the occurrence of skin disorders and dermatologically relevant skin diseases caused by these specific occupational exposures. The latter is relevant for medical advice in occupational dermatology and occupational medicine. On the basis of existing studies on welders and studies regarding occupations with "open flames" (using the example of the glassblower) it is evident that so far no reliable data exist regarding the chronic photodamage or the occurrence of UV-typical skin cancers, but instead clear evidence exists regarding the regular occurrence of acute light damage in these occupations.

Occupational skin cancer induced by ultraviolet radiation and its prevention.

Skin cancer is by far the most common kind of cancer diagnosed in many western countries and ultraviolet radiation is the most important risk factor for cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). Although employees at several workplaces are exposed to increased levels of UV radiation, skin cancer due to long-term intense occupational exposure to UV radiation is often not considered as occupational disease. The actually available evidence in the epidemiological literature clearly indicates that occupational UV radiation exposure is a substantial and robust risk factor for the development of cutaneous SCC and also clearly shows a significant risk for developing BCC. There is enough scientific evidence that outdoor workers have an increased risk of developing work-related occupational skin cancer due to natural UV radiation exposure and adequate prevention strategies must be implemented. The three measures which are successful and of particular importance in the prevention of nonmelanoma skin cancer in outdoor workers are changes in behaviour regarding awareness of health and disease resulting from exposure to natural UV radiation, protection from direct UV radiation by wearing suitable clothing, and regular and correct use of appropriate sunscreens.

[Cutaneous malignancies in occupationally-induced scars]. / Maligne Hauttumoren in beruflich verursachten Narben.

BACKGROUND: The occurrence of neoplasms in injury scars--as consequence of occupational accidents--may lead to compensation according to the statutory accident insurance regulations. According to newer regulatory attempts in occupational dermatology, certain criteria have to be met before the diagnosis of a neoplasm induced by a scar is accepted and compensation is due. MATERIAL AND METHODS: Based on a retrospective analysis of 217 dermatological claim files between 2007 and 2009 of the IPA (including 22 follow-ups), medical opinions on neoplasms developing in possible occupational scars were re-evaluated using criteria of the German social accident insurance and the Bamberg medical bulletin, part II (Bamberger Merkblatt, BM II) to see how well they qualified for recognition as an occupational or accident-related disorder. RESULTS: Three cases were identified where a neoplasm was suspected of having developed in an occupationally-related scar. One of the insured events entitled for compensation. Following the guidelines of the BM II, this case was approved as an occupational disease secondary to injuries with resultant reduction in earning capacity, whereas the others did not meet the requirements. CONCLUSIONS: Two problems in evaluating malignant tumors in occupational scars are the long latency period and the documentation of a scar. The tumor excision specimen should be histologically re-examined to document the presence of an associated scar.

Classification of skin sensitizing substances: a comparison between approaches used by the DFG-MAK Commission and the European Union legislation.

A systematic classification of substances (or mixtures of substances) with regard to various toxicological endpoints is a prerequisite for the implementation of occupational safety strategies. As its principal task the "Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area" of the "Deutsche Forschungsgemeinschaft" (DFG-MAK Commission) derives and recommends maximum workplace concentrations and biological tolerance values (MAK and BAT values) based exclusively on scientific arguments. Several endpoints are evaluated separately in detail, e.g. carcinogenicity, risks during pregnancy, germ cell mutagenicity or contribution to systemic toxicity after cutaneous absorption. Skin- and airway sensitization is also considered; the present paper focuses on these two endpoints.

[Induction of occupational leucoderma and vitiligo. Can butylated hydroxytoluene induce vitiligo similarly to p-tert-butylphenol?]. / Beruflich bedingte Leukoderme und Vitiligo. Kann Butylhydroxytoluol ähnlich dem p-tert.-Butylphenol eine Vitiligo auslösen?

BACKGROUND: While vitiligo is usually idiopathic, some cases are caused by chemicals. If occupational exposure to p-tert-butylphenol (ptBP) leads to vitiligo, the legal requirements for occupational disease Nr. 1314 can be fulfilled in Germany. Chemicals of similar structure can induce local and more widespread symmetrical depigmentation with genital involvement, making the differential diagnosis more complicated. Occupationally caused depigmentation from other chemicals can also be treated according to § 9 sec. 2 of the occupational disease regulations. MATERIALS AND METHODS: Some substances can cause leukoderma only in animals; others in animals and humans; in some cases systemic vitiligo-like changes develop. The effects on human skin cannot always be predicted from the structural analogies of the involved chemicals. RESULTS: Based on a case of occupational exposure to butyl hydroxytoluene with possible induction of vitiligo, a careful updated literature analysis of substances inducing depigmentation is presented. CONCLUSION: The literature contains discrepancies in the evidence for the ability of some substances-especially BHT-to cause vitiligo. A more exact analysis indicates that BHT does not cause vitiligo or leukoderma.

[Skin protection. From TRGS 401 to guidelines on "occupational skin protection products"]. / Hautschutz. Von der TRGS 401 bis zur Leitlinie "Berufliche Hautmittel".

The technical standards for hazardous substances (TRGS) reflect the currently achievable technical safety, occupational-medical, hygienic and scientific standards for production, distribution and handling of hazardous substances. The TRGS 401 "Risks resulting from skin contact--determination, evaluation, measures" gives important information regarding occupational hazardous exposure of the skin and the measures for prevention. A definition for wet work is given under which occlusion by moisture impermeable protective gloves and contacts to wet environments are included. Both the TRGS 401 and the AWMF S1 guidelines on "Occupational protection products" place emphasis on the fact that the protective effectiveness of topical skin products for protection, care and cleansing should be proven by in vivo methods.

The European standard series in 9 European countries, 2002/2003 -- first results of the European Surveillance System on Contact Allergies.

Since January 2001, the European Surveillance System on Contact Allergies (ESSCA), supported by European Union funding (contract QLK4-CT-2001-00343), has started to collect patch-test data. This comprises a standardized clinical history and the patch-test results using the European standard series, from 17 centres in 9 European countries listed above. In 2002 and 2003, 10 511 patients' test results have been pooled and analysed. The anamnestic data partly reflect the subspecialties of some centres. The most common allergen was nickel sulfate (17.3%); however, large international variations were observed. The prevalence of contact allergy to Myroxylon pereirae resin (balsam of Peru) (5.8%) is coming close to the frequency found with the fragrance mix (6.4%). Regarding contact allergy to chromium compounds, different frequencies were noted in the 2 centres focused on occupational dermatitis (2.3% in the FIOH versus 7.4% in the Nofer Institute). These most likely reflect the beneficial effect of addition of ferrous sulfate in one, but not the other country. As differences may partly be due to different patch-test reading, standardization may need to be refined further. By providing post-marketing surveillance in the field of contact allergy, ESSCA will meet its objective of increased consumer safety across Europe.

Painful stimuli evoke itch in patients with chronic pruritus: central sensitization for itch.

BACKGROUND: Central sensitization for pain is important for patients with chronic pain. The authors investigated a possible role of central sensitization for itch in patients with chronic pruritus. METHODS: Noxious stimuli were applied in lesional and visually nonlesional skin areas of 25 patients with atopic dermatitis, in lesional skin areas of 9 patients with psoriasis vulgaris, and in 20 healthy subjects. The stimuli included mechanical pinpricks, electrical stimuli, contact heat, and injection of low-pH solution. Intensities of itch and pain were assessed separately on a numeric rating scale. RESULTS: All the noxious stimuli primarily evoked pain in control subjects and patients with psoriasis vulgaris. In patients with atopic dermatitis, however, itch was evoked instead of burning pain. In their lesional skin, itch was the predominant sensation. Chemical stimuli evoked intense itch in lesional and visually healthy skin areas (the area under the curve of itch rating compared with the control, mean +/- SEM, 668 +/- 166 and 625 +/- 192 vs 38 +/- 23; p < 0.001; p < 0.01). Chemically induced itch also was observed in healthy subjects after a conditioning histamine stimulus of 15 minutes, but not after a conditioning histamine stimulus of 2 minutes. CONCLUSION: The chronic barrage of pruriceptive input may elicit central sensitization for itch so that nociceptive input no longer inhibits itch but on the contrary is perceived as itch. In contrast to the well-known A-fiber-mediated alloknesis and hyperknesis, this type of central sensitization appears to be elicited by C-nociceptors.

[Education programs on atopic eczema. Design and first results of the German Randomized Intervention Multicenter Study]. / Neurodermitisschulung. Konzept und aktueller Stand der German Randomized Intervention Multizentre Study.

Atopic eczema (AE) is a common, chronically relapsing, inflammatory skin disease with an early onset during infancy associated with a high loss of quality of life and socioeconomic burden. In the past few years, an Atopic Eczema Prevention Program was established to improve disease management and the quality of life of patients with atopic eczema. In Germany, the Task Force on Education Programs for Atopic Eczema (AGNES = Arbeitsgemeinschaft Neurodermitis Schulung) for children, youths, and parents was founded as well as the Task Force on Dermatological Prevention (ADP) for adults. These groups ensure structure and process quality of the prevention programs and organize train-the-trainer workshops. In a randomized prospective controlled trial (the German Randomized Intervention Multicenter Study = GRIMS), we are currently comparing the effectiveness of an atopic eczema group intervention program in (1) parents of atopic eczema children aged 0-7 years, (2) parents and children 7-12 years old, and (3) youths with AE aged between 13 and 18 years. The groups were randomized and compared with a waiting control group. The design and first results will be reported.

[Sensitization to tea tree oil in Germany and Austria. A multicenter study of the German Contact Dermatitis Group]. / Sensibilisierung auf Teebaumöl in Deutschland und Osterreich--Eine multizentrische Studie der Deutschen Kontaktallergiegruppe.

BACKGROUND AND AIM: Tea tree oil, a distillation product of the Australian tea tree (Melalence alternitolia) is increasingly used as an alternative remedy for various dermatological diseases. Tea tree oil contains several allergenic monoterpenes and sesquiterpenes. In this multicenter study it was evaluated, whether the increasing use of tea tree oil has lead to an increased frequency of sensitization in Germany and Austria which would justify its inclusion into the standard series. PATIENTS AND METHOD: For patch testing a standardized tea tree oil was used, dissolved 5% in diethylphtalate (DEP). Consecutive patients of 11 dermatological departments in Germany and Austria were tested. Readings were taken on day 2 and 3 according to the guidelines of the German Contact Dermatitis Research Group (DKG). RESULTS: 5% tea tree oil was positive in 36/3375 patients (1.1%). Sensitization frequencies showed great regional variations and ranged from 2.3% (Dortmund), 1.7% (Buxtehude), 1.1% (Essen), 0.7% (Graz), to 0% (Berlin, Vienna). 14/36 patients (38.9%) also showed a positive patch test reaction to oil of turpentine. CONCLUSION: Our results show that tea tree oil is an important contact allergen for some centers. It should be tested, if medical history suggests its previous use. Considering the great regional differences in frequencies of sensitization its inclusion into the standard series is not recommended yet.

When should a substance be designated as sensitizing for the skin ('Sh') or for the airways ('Sa')?

In the List of MAK and BAT Values compounds are designated with 'Sa' ('sensitizing for the airways') or 'Sh' ('sensitizing for the skin') if, according to scientific evidence, they are allergens. Mainly based on suggestions by a WHO working group and based on our own experience, extended criteria have been elaborated by the working group 'skin and allergy' of the Commission of the Deutsche Forschungsgemeinschaft for the Investigation of Health Hazards of Chemical Compounds in the Work Area, which are presented in this article. They serve as guidelines for deciding which substances have to be labelled 'Sa' and 'Sh', respectively, for the prevention of sensitization and subsequent allergic diseases in workers. Although in some special cases their strict application may not be deemed necessary or possible, the proposed new criteria should be used to make the procedure of classification of substances: 1) more rational, 2) more consistent, 3) more comprehensible, and 4) more transparent. This paper informs readers working scientifically or administratively in this field and invites a critical discussion of the issue.

High molecular compounds (polysaccharides and proanthocyanidins) from Hamamelis virginiana bark: influence on human skin keratinocyte proliferation and differentiation and influence on irritated skin.

Although extracts from Hamamelis bark have long been used in therapy of skin diseases and in cosmetic formulas there are only few pharmacological investigations verifying the activity of distinct Hamamelis bark constituents. Therefore two major classes of constituents, namely polymeric proanthocyanidins and polysaccharides were isolated from Hamamelis bark and tested concerning their influence on proliferation and differentiation of cultured human keratinocytes. While the polysaccharide fraction, consisting mainly of arabans and arabinogalactans, did not effect human keratinozytes, the proanthocyanidins strongly increased the proliferation of the cells, while the differentiation was not influenced significantly. Within a preliminary cumulative in vivo study on SLS-irritated skin, proanthocyanidins (ProcyanoPlus) were proven to reduce transepidermal water loss and erythema formation. Furthermore, a clinical scoring indicated that procyanidins can influence irritative processes significantly.

A strikingly constant ratio exists between Langerhans cells and other epidermal cells in human skin. A stereologic study using the optical disector method and the confocal laser scanning microscope.

Langerhans cells play an important part in the immune surveillance of the human epidermis. Therefore, a certain distribution and numerical relationship to other epidermal cells can be expected. To quantify epidermal Langerhans cells population extensive studies have been performed using two-dimensional quantification methods on vertical sections or epidermal sheet preparations. Whereas methods using vertical sections were complicated considerably by the sampling procedure, the dendritic shape, and the suprabasal, nonrandom distribution of Langerhans cells, epidermal sheet preparations have their limitations regarding the numerical relationship of Langerhans cells to total epidermal cells and the epidermal morphology as such. In order to improve the validity of data the three-dimensional dissector method combined with confocal laser scanning microscopy has been applied to quantify the number of Langerhans cells and other epidermal cell nuclei per volume unit in cryosections of 24 punch biopsies of normal breast skin of eight women. Furthermore, the ratio of Langerhans cells to other epidermal cells, their number per biopsy, and per skin surface area were calculated. To minimize the bias by shrinkage the reference volume was estimated using Cavalieri's principle. A constant ratio of one Langerhans cells to 53 other epidermal cells was identified in breast skin (interindividual correlation coefficient: 0.952, p < 0.0001). Thus, Langerhans cells represent 1.86% of all epidermal cells; however, a wide interindividual range was found for the number of Langerhans cells per mm2 (912-1806; mean +/- SD 1394 +/- 321) and other epidermal cells per mm2 (47,315-104,588; mean +/- SD 73,952 +/- 19,426). This explains the conflicting results achieved by conventional morphometric assessments relating cell numbers to skin surface area, ignoring the varying thickness of the epidermis. The surprisingly constant relationship of Langerhans cells to other epidermal cells stresses the hypothesis of an epidermal Langerhans cells unit where one Langerhans cells seems to be responsible for the immune surveillance of 53 epidermal cells.

Incidence of work-related hand eczema during apprenticeship: first results of a prospective cohort study in the car industry.

Data on the incidence and prevalence of occupational contact dermatitis (OCD) are scarce, and most of our knowledge about OCD is derived from clinical case reports or clinical studies of in-and out-patients. Therefore, we investigated in the epidemiological, prospective Audi cohort study (PACO study) the incidences of work-related hand eczema in different apprenticeships of Audi AG. In total, 2078 apprentices were investigated at the start of their apprenticeship and systematically followed up over a 3-year period. At the end of the study, information on 2042 (98.2% follow-up) apprentices was available. The 1-year cumulative incidences of hand eczema were 9.2% (95%-confidence interval 7.8-10.7) in metalworkers, 8.8% (95%-CI 7.0-10.7) in other blue-collar workers, and 4.6% (95%-CI 2.3-8.1) in white-collar apprentices. The 3-year cumulative incidences of hand eczema were 15.3% (95%-CI 13.6-17.2) in metalworkers, 14.1% (95%-CI 11.8-16.5) in other blue-collar workers, and 6.9% (95%-CI 4.0-10.9) in white-collar apprentices. In females, the cumulative incidence of hand eczema was higher compared to men (1-year incidence 10.1%, 95%-CI 7.7-13.0, versus 8.3%, 95%-CI 7.1-9.5; 3-year incidence 16.1%, 95%-CI 13.1-19.5 versus 13.6%, 95%-CI 12.2-15.2). In some occupations, like cooks, tool mechanics, milling cutters and varnishers, the incidence of hand eczema was significantly increased. In those occupations, however, no job change was necessary, and no notifiable occupational contact dermatitis occurred. The incidence was not uniformly distributed over the 3-year period. Within the first 6 months, a particularly high rate of hand eczema occurred, which then declined and remained steady at a lower rate over the 2nd and the 3rd years. The results of our study give important suggestions for preventive measures at the workplace and effective occupational pre-employment advices.