Skin allergy to chemicals

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Skin allergy to chemicals clinical, epidemiological and public health perspectives Jeanne Duus Johansen National Allergy Research Centre Department of Dermato allergology Copenhagen University Hospital Gentofte Denmark

Exposure Wide spread skin exposure to chemicals Intended (e.g. cosmetics) Unintended (e.g. work place) Many chemicals are allergens Preservatives Glues Dyes Fragrances Metals

Epidemiology of skin (contact) allergy 21.6% of the European population is sensitized to one or more chemcials Women: Men 2:1 Debut at young age: 12 16 years: prevalence 15% Allergic eczema in 5 10% /year A frequent work related disease Thyssen JP, Linneberg A, Menné T, Johansen JD. Contact Dermatitis. 2007 Nov;57(5):287 99. Moertz CG et al. Acta Derm Venereol 2002:82:359 361

Allergic eczema Fragrances/preservatives Hair dyes shoes Occupational exposures

Environment/genes? Twin studies: A mainly environmental disease No specific genes identified Susceptible groups? Multiple allergies Weak allergens Enzyme systems in the skin Skin barrier defects Frequency 8% 7% 6% 5% 4% 3% 2% 1% 0% Cumulative environmental exposure needed Multiple contact allergies: dependency of age and sex 0 10 20 30 40 50 60 70 80 90 Age Total Men Women Carlsen B et al. Contact Dermatitis 2007

Preventable Dose response Thresholds in induction and elicitation Used in nickel regulation: Consumer items in close contact with skin Nickel release limit <0.5 µg/cm 2 /week Fischer LA et al. Contact Dermatitis 2009 Decrease in nickel allergy in young eczema patients Schnuch, A. et al. Contact Dermatitis 2003

Further trends Trend of sensitization to nickel in women (aged 1 30 years) (1992 2007) 38 36 % Nickel-positive 34 32 30 28 26 24 22 20 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 Year EU-Directive Schnuch A, Wolter J, Geier J, Uter W. Contact Dermatitis 2011; in print

Cosmetics Fragrance ingredients 1 4% of the population 10% of patients Causative products creams deodorants perfumes Too high levels of skin allergens in products Cocktails of allergens Uter W, Geier J, Schnuch A, Frosch PJ. J Eur Acad Dermatol Venereol. 2007 Mar;21(3):374 9. Nardelli A, Carbonez A, Ottoy W, Drieghe J, Goossens A. Contact Dermatitis. 2008 Mar;58(3):134 41

Fragrance allergy and daily living Self perceived effect on daily living? N=147 with fragrance allergy (Gentofte Hospital, 18 months) Due to fragrance contact allergy I have to take special precautions 67.5% I often have eczema, itch 47.0% I have had sick leave 17.1% My daily living is significantly affected 45.3% Lysdal S, Johansen JD. Contact Dermatitis 2009:61:320 324

General population N=3460 Year 2006 Patch test (FM I) Questionnaire Positive patch test to a mixture of 8 fragrance ingredients were positively associated with: I. Dermatitis to cosmetic products (past 12 months): OR: 3.5 (CI 2.0 6.2) II. Dermatitis to cosmetics lead to medical consultations Or: 3.4 ( CI1.8 6.2)

Preservation Needed to avoid contamination of water based products cosmetics and occupational products Lundov M. Ph.d. thesis 2011

Skin allergy to preservatives % Total prevalence Thyssen JP et al. CD 2010: 62 102 108

Skin allergy to preservatives German data Schnuch A. et al. 2011: BJD:in press

Hair dye allergy Gudbjerg P. Ugeskr. For Læger 2003:11:165(33)

Hair dyes Contact allergy caused by hair dyes is an important health problem often causing acute and severe dermatitis Many hair dye substances are extreme or strong sensitizers. These may not be safe for the consumer

Ingredient label examined: 120 out of 122 oxidative hair dye products contained potent skin sensitizers More than 80% contained at least four such substances 16

Exposure to hair dyes 75% of adult women have dyed their hair Sosted H.Br. J. Dermatol. 2005: 153, 132 135 Girls (15 18 years) n=1062 population based: 82.3% have dyed their hair 13.1 years age at first hair dye 3.7 hair dyes/ year Adverse effects: 2.9% oedema after hair dying 9.4% report rash from hair dyes Extract from: Bregnhøj A, 2011: Contact Dermatitis:64:85 9

Occupational exposure: hairdressers Exposure to hair dye in saloons from Dying Cutting Background Wrong use of gloves Lind ML et al Ann Occup Hyg. 2005 Aug;49(6):473 80 Cohorte of 5.324 hairdressers: 44.3% stopped in profession Mean time in profession: 8.4 years Half of these because of hand eczema 70% says it started as apprentice Lysdal S et al.contact Dermatitis 2011: submitted

Occupational skin disease: Represent up to 25 % of all occupational illness Account for 90% of all work related problems in the age group of 15-25 years Diepgen TL, Kanerva L.Eur J Dermatol. 2006 May Jun;16(3):324 30. European Agency for Safety and Health and Work. Observatory report 2008

Consequences Hand eczema Chronic disease Skin allergy (positive patch test): Risk factor for bad prognosis The determinants of chronic disease not known 15 year follow up: 2 out of 3 have had symptoms Meding B et al. Contact Dermatitis 2005:53:308 313 Br J Derm 2005:152:975 980; J. Invest Dermatol 2005:893 7 John SM. Epos 2010

Consequences Sick leave: 7% Total median: 38 weeks Decrease in nickel allergy in young eczema patients Medical attention Treatment 50% corticosteroids Psycho social consequences Disturbances: 96% Occupational changes Estimated direct expenses of occupational disease > 5 billion Euro/years Schnuch, A. et al. Contact Dermatitis 2003 Reduction in new cases estimated value in DK: 1.3 billon Euro/20 years Meding B et al. Contact Dermatitis 2005:53:308 313 Br J Derm 2005:152:975 980; J. Invest Dermatol 2005:893 7 John SM. Epos 2010

Conclusions Skin allergy is frequent Caused by a range of different exposures Frequent problems / severe problems Impact on the individual and society Can be reduced/prevented

Gaps of knowledge Data on a European level Trends Causative exposures (consumers/occupational) Susceptible groups? Role of skin enzymes Role of skin barrier Genetics/gender Determinants of chronic disease Strategy for using preservative Exposure data: cocktails of allergens, many sources Risk assessment strategy and risk reduction : preventive measures

This paper was produced for a meeting organized by Health & Consumers DG and represents the views of its author on the subject. These views have not been adopted or in any way approved by the Commission and should not be relied upon as a statement of the Commission's or Health & Consumers DG's views. The European Commission does not guarantee the accuracy of the data included in this paper, nor does it accept responsibility for any use made thereof.