A follow-up study of course and development of atopic dermatitis, hand eczema, and allergic contact dermatitis in young Danish adults (TOACS cohort).

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1 A follow-up study of course and development of atopic dermatitis, hand eczema, and allergic contact dermatitis in young Danish adults (TOACS cohort). Name of applicant: MD, Ph.d. Charlotte Gotthard Mørtz Department of Dermatology Odense University Hospital DK-5000 Odense C Scientific members of the project group: Professor, dr.med., Klaus Ejner Andersen Professor, dr.med. Carsten Bindslev-Jensen MD, Ph.d. Jens Martin Lauritsen Background: Hand eczema is a common skin disease with a one-year period prevalence around 10% in the general population 1 and a lifetime prevalence of approximately 17% 2. Hand eczema is often a chronic recurrent disease with major consequences for the patient with long lasting treatment, affecting daily life and ability to work. In exposed occupations (e.g. nurses, cleaners) the frequency is increases up to 30% 3. The prevalence is double in women compared to men 1. Hand eczema is a multifactorial disease caused by irritants, often in combination with contact allergy and endogenous factors. Hand eczema is one of the 3 most common occupational diseases in Denmark. The number of notified occupational skin diseases is approximately per year 4, and they rank 1st among all recognized occupational diseases 4. Occupational dermatitis most often affects young adults early in their working life and causes considerable problems and discomfort for the individual, sick leave, medical expenses, doctors visits and the cost for the society is significant do to sick leave, change of occupation, rehabilitation, retirement and compensations. The estimated total costs amount to around 1 billion DDK each year. The TOACS-cohort (The Odense Adolescents Cohort Study) was established in Odense in 1995 and consist of th grade school children (mean age 14.1 years) in 40 of 43 schools in the municipality of Odense. The cohort was examinated for the first time in 8 th grade to evaluate the prevalence of eczema and allergy before the adolescents leave school (phase one). Furthermore, selected groups was re-examinated in 9 th grade (phase 2). Phase one and two formed the basis of one Ph.d. and resulted in 5 publications in international journals 5-9.

2 Phase one ( ) was conducted as a cross-sectional study and included questionnaire, interview and clinical examination, blood sampling for IgE measurements (CAP FEIA R ) and diagnostic patch tests (TRUE Test R including nickel dilution series). Phase two ( ) was a case-control study among selected school children (n=702) and included interview, clinical examination, skin prick tests (Soluprick R, fresh foods) and skin barrier function tests. The proportion of participation in the different parts of the study was very high. The lifetime prevalence of atopic dermatitis was 21.3%, the lifetime prevalence of inhalant allergy was 17.7% (allergic asthma 6.9%, allergic rhinitis 15.7%) and the lifetime prevalence of hand eczema was 9.2% among 8 th grade school children 8. The point prevalence of contact allergy was 15.2% with a significant predominance in girls. Present or past allergic contact dermatitis was found in 7.2% 7. Both for Type I and Type IV sensitisation a conciderable proportion was sensitised without clinical relevance at that time 5;7. This application concerns phase 3, which is a follow-up study of the 1254/1501 (83.5%) who gave informed consent to be contacted later on. The follow-up is planned after years e.g to follow the course of atopic diseases, hand eczema and contact dermatitis taking the occupational exposure into consideration. The main goal for the follow-up study is risk assessment in relation to education and occupation for development of hand eczema and contact allergy in those adolescents with atopic dermatitis, inhalant allergy, hand eczema and contact allergy diagnosed 10 years earlier. Aims: 1. To estimate the prevalence of hand eczema (allergic, irritant, endogenous) and contact allergy among young adults. 2. To investigate the association between present hand eczema/ contact allergy and previous atopic dermatitis, inhalant allergy, contact allergy and hand eczema. 3. To investigate the association between present hand eczema/ contact allergy and occupation, wet and dry work and use of gloves. 4. To evaluate if the risk of hand eczema is increased among young adults with both hand exposed occupation in adulthood and atopic dermatitis/ inhalant allergy/ hand eczema/ contact allergy in childhood. 5. To evaluate if the degree of nickel allergy in childhood is associated to later development of hand eczema. 6. To investigate if the skin barrier function in adolescence can predict later development of hand eczema.

3 7. To follow the course and development of atopic diseases, eczema and allergic contact dermatitis among those with positive allergy tests in adolescence without known clinical relevance in school age. Population: Young adults who took part in phase one in 1995/96 and gave informed consent to be contacted again after about 10 years (n=1254). Method. A letter with information about the study, a consent form and a questionnaire is sent to all individuals from the TOACS population (n=1254). All who agree to participate in phase 3 receive a patch test (TRUE test R standard and nickel dilution series) to put on the back at home. Test readings are done at day 3 by the investigator or the allergy nurse from the project group. Furthermore, a clinical examination for skin disease is offered together with a blood test for IgE analyses and skin prick tests, that are performed according to current guidelines 10;11. The blood sample and skin prick tests are tested for inhalant allergens, food allergens, malassezia furfur and latex. The participants are examined preferably at the Department of Dermatology, Odense University Hospital. The participants will receive the results of the patch test and skin prick test. The clinical examination for each participant will take approximately 45 minutes. The data will be entered twice in the database and merged with the primary TOACS-database. Data will be validated in relation to content and completeness for possible selective follow-up mechanisms. The relative risk for developing hand eczema and contact allergy in the different groups in relation to pre-defined exposure categories are estimated in crude, stratified and controlled regression analysis with thorough investigation of possible confounding and effect modification. Ethics: A renewed approval from the ethics committee and Registertilsynet to re-examine the TOACS cohort will be obtained. Organisation: The study is performed at the Department of Dermatology, Odense University Hospital. The examinations are performed by the same M.D. (Charlotte G. Mørtz) assisted by the same allergy nurse as 10 years ago. The same group of scientific supervisors as 10 years ago will support the investigator in conducting the study and analysing data and publishing the results.

4 All data from phase 1 & 2 are stored at Danish Data Archives, Islandsgade 10, DK-5000 Odense, study number DDA-5975 and access is open for the study group. The physical facilities for the study are available at the Department of Dermatology, and the necessary techniques are routines in the department. For TOACS individuals participating in the study and who are living in Jutland or Zealand the clinical examination can take place at the Dermatological Departments in Aarhus or Copenhagen. The duration of the study is one year with one post doc position. This follow-up study is unique because there are no prospective clinical epidemiological studies on the course and development of contact dermatitis/ contact allergy/ hand eczema in populations of unselected young adults. Furthermore, it is of major importance for the quality of the study that the same persons are performing the study both in and in the follow-up. Reference List 1. Meding B, Järvholm B. Hand eczema in Swedish adults - change in prevalence between 1983 and J Invest.Dermatol 2002; 118: Meding B, Järvholm B. Incidence of hand eczema - a population-based retrospective study. J Invest.Dermatol 2004; 122: Smit HA, Burdorf A, Coenraads PJ. Prevalence of hand dermatitis in different occupations. Int.J.Epidemiol. 1993; 22: Halkier-Sorensen L. Occupational skin diseases. Contact Dermatitis 1996; 35: Mortz CG, Lauritsen JM, Andersen K.E. et al. Type I sensitization in adolescents: prevalence and association with atopic dermatitis. The Odense Adolescents Cohort study on Atopic Diseases and Dermatitis (TOACS). Acta Derm.Venereol. 2003; 83: Mortz CG, Lauritsen JM, Bindslev-Jensen C et al. Nickel sensitization in adolescents and association with ear piercing, use of dental braces and hand eczema. The Odense Adolescents Cohort study on Atopic Diseases and Dermatitis (TOACS). Acta Derm.Venereol. 2002; 82:

5 7. Mortz CG, Lauritsen JM, Bindslev-Jensen C et al. Contact allergy and allergic contact dermatitis in adolescents: prevalence measures and associations. The Odense Adolescents Cohort study on Atopic Diseases and Dermatitis (TOACS). Acta Derm.Venereol. 2002; 82: Mortz CG, Lauritsen JM, Bindslev-Jensen C et al. Prevalence of atopic dermatitis, asthma, allergic rhinitis, and hand and contact dermatitis in adolescents. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis. Br J Dermatol 2001; 144: Mortz C.G., Andersen K.E., Bindslev-Jensen C. The prevalence of peanut sensitization, and the association to pollen sensitization in a cohort of unselected adolescents. Pediatr.Allergy Immunol. 2005; Accepted. 10. Rycroft RJG, Menne T, Frosch PJ. Textbook of contact dermatitis, 2 edn. Berlin, Heidelberg: Springer- Verlag, 1995: Dreborg S. Skin tests used in type I allergy testing. Allergy 1989; 44: 1-59.

6 TOACS Detaljeret budget (2007 niveau) Løn: Post doc (12 måneder) for afdelingslæge, ph.d. Charlotte G. Mørtz (37 timer pr. uge inkl. pension, ferie) Sygeplejerske (12 måneder) (forskningssygeplejerske løntrin 6-37 timer pr. uge, pension, ferie) DKr DKr Driftsomkostninger: TRUE test panel 1&2 og nikkeltest til 1254 tests DKr Soluprick ekstrakter til 1254 tests DKr CAP FEIA analyser til 1254 tests DKr Yderligere materiale til blodprøver, priktest, lappetest e.g. kanyler, glas ect DKr Kontorhold DKr Database DKr Sum Overhead/administration 3.1% DKr DKr Total DKr Modtaget støtte fra Aage Bangs Fond Dkr Total Dkr

7 Charlotte Gotthard Mørtz, afdelingslæge, Ph.D. Dermatologisk afdeling I, Odense Universitetshospital Sdr. Boulevard 29 DK Odense C charlotte.moertz@ouh.regionsyddanmark.dk Curriculum vitae Personlige data: Afdelingslæge, Ph.D. Charlotte Gotthard Mørtz, født Nielsen. Født den i Glostrup. Gift med Ejvind Mørtz. 2 børn: Kathrine 11 år og Anne-Sofie 7 år. Adresse, privat: Kærsagerhaven Odense S. Telefonnummer: , Nuværende ansættelse: Afdelingslæge, Dermatologisk afdeling I, Odense Universitetshospital, Sdr. Boulevard 29, DK-5000 Odense C Uddannelse: 1987: Matematisk-naturfaglig studentereksamen fra Kalundborg Gymnasium (gennemsnit 9,6) : Diplomstuderende ved Det Sundhedsvidenskabelige Fakultet, Odense Universitet under Dermato-venerologisk afdeling I, Odense Universitetshospital. Projekttitel: Lipiders betydning for hudens barrierefunktion. Afsluttet diplomstudiet med eksamen i medicinsk forskning (27/4-1994). 1995: Medicinsk embedseksamen juni 1995, Odense Universitet (gennemsnit 9,9) : Ph.d. studerende ved Det Sundhedsvidenskabelige Fakultet, Odense Universitet under Dermato-venerologisk afdeling I, Odense Universitetshospital. Projekttitel: Forekomst af atopisk eksem og kontakteksem blandt skolebørn i 8. klasse i Odense kommune. (Under ansættelsen 9 måneders barselsorlov). 1999: Reservelæge, medicinsk afdeling, Ringsted sygehus ( ). Turnus. 2000: Barselsorlov, forældreorlov ( ). Ph.d.-graden (26/5-2000).

8 2001: Reservelæge, parenkymkirurgisk afdeling, Slagelse sygehus ( ). Turnus. Praksisreservelæge, Lægernes Hus, Norvangen, Korsør ( ). Turnus. 2002: Introduktionsstilling i dermato-venerologi, Dermato-venerologisk afdeling I, Odense Universitetshospital ( ) : Kursusstilling i dermato-venerologi, Region Syd ( ) : Kursuseservelæge, medicinsk afdeling, Sygehus Fyn, Svendborg Sygehus : Kursusreservelæge, Dermato-venerologisk afdeling I, Odense Universitetshospital : Kursusreservelæge, Dermato-venerologisk afdeling S, Århus Sygehus : 1. reservelæge, Dermato-venerologisk afdeling S, Århus Sygehus : 1. reservelæge, Hudklinikken, Rådhustorvet 4, 7000 Vejle : 1. reservelæge, Dermato-venerologisk afdeling I, Odense Universitetshospital : Vikar for afdelingslæge, Dermato-venerologisk afdeling I, Odense Universitetshospital

9 : Afdelingslæge, Dermato-venerologisk afdeling I, Odense Universitetshospital 2007: Speciallæge i Dermato-venerologi (31/1-2007). Publikationer: Priser: Foredrag: Vejlederfunktion: Andet: 14 fra , heraf 11 i internationale peer reviewed tidsskrifter og 3 i ugeskrift for læger. Schering-Plough prisen for året 2001 (Dansk Selskab for Allergologi) Mere end 20 foredrag indenfor dermatologi og allergologi ved internationale kongresser og danske møder. Desuden undervisning af bl.a yngre læger, praktiserende læger, sygeplejersker, sundhedsplejersker, ved A-kursus samt på patientskole (eksemskole) både lokalt og i de 5 regioner. Vejleder for cand. med., ph.d. Morten Østerballe i Ph.D. -projektet med titlen: Prevalence of adverse reactions to food in danish children 3 years of age and in their relatives (siblings and parents). Afsluttet Med i Organizing committee for 14th Meeting of the European Research Group on Experimental Contact Dermatitis, 22/5-24/5-97, Odense, Danmark, og planlagt 3 danske møder for yngre dermatologer 2003, 2005, Med i Efteruddannelsesudvalget under Dansk Dermatologisk Selskab Bestyrelsesmedlem i Foreningen af Yngre Dermatologer fra Suppleant i bestyrelsen i Dansk Selskab for Allergologi Underviser/ ansvarshavende for Eksemskolen, OUH Publikationsliste 1997: Mortz CG, Andersen KE, Halkier-Sørensen L. The efficacy of different moisturizers on barrier recovery in hairless mice evaluated by noninvasive bioengineering methods. Contact Dermatitis 1997, 36, : Mortz CG, Andersen KE. Allergic contact dermatitis in children and adolescents. A review. Contact dermatitis 1999, 41, : Mørtz CG, Bygum A. Asymmetrisk perifleksuralt eksantem i barnealderen. Ugeskr Læger 2000, 162 ;

10 Nielsen NH, Mørtz CG. Epidemiologien ved kontakteksem. Ugeskr Læger 2000, 162 ; : Mortz CG, Lauritsen JM, Bindslev-Jensen C, Andersen KE. Prevalence of atopic dermatitis, asthma, allergic rhinitis, and hand and contact dermatitis in adolescents. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis. Br J Dermatol 2001;144: : Mortz CG, Lauritsen JM, Bindslev-Jensen C, Andersen KE. Nickel sensitization in adolescents and association with ear piercing, use of dental braces and hand eczema. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). Acta Derm Venereol. 2002;82(5): Mortz CG, Lauritsen JM, Bindslev-Jensen C, Andersen KE. Contact allergy and allergic contact dermatitis in adolescents: prevalence measures and associations. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). Acta Derm Venereol. 2002;82(5): : Morts CG, Lauritsen JM, Andersen KE, Bindslev-Jensen C. Type I sensitization in adolescents: prevalence and association with atopic dermatitis. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). Acta Derm Venereol 2003; 83: Bygum A, Mortz CG, Andersen KE. Atopy patch tests in young adult patients with atopic dermatitis and controls: dose-response relationship, objective reading, reproducibility and clinical interpretation. Acta Derm Venereol 2003; 83: : Osterballe M, Hansen TK, Mortz, CG, Bindslev-Jensen C. The clinical relevance of sensitization to pollen-related fruits and vegetables in unselected pollen-sensitized adults. Allergy 2005;60: Osterballe M, Hansen TK, Mortz CG, Høst A, Bindslev-Jensen C. The prevalence of food hypersensitivity in an unselected population of children and adults. Pediatr Allergy Immunol 2005; 16: Mortz CG, Andersen KE, Bindslev-Jensen C. The prevalence of peanut sensitization, and the association to pollen sensitization in a cohort of unselected adolescents. The Odense Adolescence Cohort Study on Atopic Diseases and Dermatitis (TOACS). Pediatr Allergy Immunol 2005; 16: : Mørtz CG, Deleuran M. Granulomatøs perioral dermatitis i barnealderen (CGPD) hos et adoptivbarn fra Madagaskar. Ugeskr Læger 2008; 170: 352.

11 Mortz CG, Andersen KE. New aspects in allergic contact dermatitis. Curr Opin Clin Immunol 2008, in press.