Skin diseases in Norway and cutaneous squamous cell carcinoma in four Nordic countries: The role of occupation and occupational exposures A population-based study Jose Hernán Alfonso Dep. of occupational Medicine and Epidemiology National Institute of Occupational Health Oslo, Norway 2016 © Jose Hernán Alfonso, 2016 Series of dissertations submitted to the Faculty of Medicine, University of Oslo ISBN 978-82-8333-279-7 All rights reserved. No part of this publication may be reproduced or transmitted, in any form or by any means, without permission. Cover: Hanne Baadsgaard Utigard. Print production: Reprosentralen, University of Oslo. 3| “...Now and then I have noticed that bakers have swollen, aching hands. Everyone in this trade gets rough hands by kneading the dough. A baker just has to show his hands to reveal this trade. No other tradesman has similar hands". “DeMorbisArtificum” BernardoRamazzini(1633Ͳ1744) Thisphotographyofabaker´shandwasacourtesyfromDr.M.N.Crepy.Availableat: http://www.atlasdedermatologieprofessionnelle.com/index.php/Boulanger 4| Committeemembers 1. Opponent:ProfessorÅkeSvensson DepartmentofOccupationalandEnvironmentalDermatology. FacultyofMedicine,UniversityofLund,Sweden͘ 2. Opponent:ProfessorMariaAlbin DepartmentofOccupationalandEnvironmentalMedicineFaculty ofMedicine,UniversityofLund,Sweden͘ InstituteofEnvironmentalMedicine.KarolinskaInstitutet,Sweden. Committeeadministrator:AssociateprofessorAnneOlaugOlsen DepartmentofRheumatology,DermatologyandInfectiousDiseases.OsloUniversity Hospital. InstituteofClinicalMedicine,FacultyofMedicine,UniversityofOslo,Norway͘ 5| CONTENTS ACKNOWLEDGEMENTS...............................................................................................................11 Agradecimientos.........................................................................................................................13 PREFACE......................................................................................................................................15 LISTOFPAPERS...........................................................................................................................17 SUMMARY...................................................................................................................................19 Resumen...............................................................................................................................................23 LISTOFABBREVIATIONS.............................................................................................................27 CHAPTERI:INTRODUCTION.......................................................................................................29 1.1NorwegianstudiesonthetopicofworkͲrelatedskindiseases............................................29 Thefirststudies....................................................................................................................................29 Systematicliteraturesearch.................................................................................................................30 1.2PopulationͲbasedstudiesonoccupationandskindiseases.................................................33 1.3Conclusionofthesystematicliteraturesearch.......................................................................40 1.4Thesisoutline...............................................................................................................................40 CHAPTERII:AIMS........................................................................................................................43 2.1Researchquestions.....................................................................................................................43 2.2.Aims..............................................................................................................................................44 CHAPTERIII:THEORETICALBACKGROUND................................................................................45 3.1Thehealthyskin..........................................................................................................................45 3.2DefinitionofworkͲrelated/occupationalskindisease...........................................................48 3.3ClassificationofworkͲrelatedskindiseases............................................................................48 3.4Irritantcontactdermatitis..........................................................................................................50 Pathogenesis........................................................................................................................................51 Cumulativeirritativecontactdermatitis..............................................................................................51 Hardeningphenomenon......................................................................................................................52 3.5Allergiccontactdermatitis.........................................................................................................52 3.6Skincancer...................................................................................................................................53 6| Definitionandnomenclature...............................................................................................................53 Latencyperiod......................................................................................................................................53 Recognitionasanoccupationaldisease...............................................................................................54 Associationsbetweenoccupation,occupationalexposures,andskincancer.....................................54 Cutaneoussquamouscellcarcinoma...................................................................................................56 RegistrationofcutaneoussquamouscellcarcinomainFinland,Iceland,Sweden,andNorway........56 IncidenceofcutaneoussquamouscellcarcinomaintheNordiccountries.........................................57 3.7DeterminantsofworkͲrelatedskinproblems,diseases,andcutaneoussquamouscell carcinoma....................................................................................................................................59 3.7.1Endogenousfactors.................................................................................................................59 Atopicdermatitis.................................................................................................................................59 Filaggrinmutations...............................................................................................................................60 Othergeneticandindividualsusceptibilityfactors..............................................................................61 Age........................................................................................................................................................61 Sex........................................................................................................................................................62 Ethnicity................................................................................................................................................62 3.7.2Exogenousfactors:Occupationalexposures.......................................................................62 Wetwork..............................................................................................................................................62 Gloveocclusion....................................................................................................................................63 Skinexposurewithchemicalproducts.................................................................................................63 Skinexposuretobiologicalagents.......................................................................................................65 Skinexposuretomechanicalfactors....................................................................................................66 Skinexposuretophysicalfactors.........................................................................................................66 Someremarks.......................................................................................................................................68 3.8SkinexposuresandskinproblemsinthegeneralworkingpopulationofNorway..............69 3.9SocioeconomicimpactofworkͲrelatedskindiseases..........................................................71 SickleaveduetoworkͲrelatedskindiseasesͲmainlycontactdermatitisͲ..........................................72 PhysicianͲcertifiedsickleaveinNorway..............................................................................................73 CHAPTERIV:MATERIALANDMETHODS...................................................................................77 4.1Studydesign.................................................................................................................................78 4.2.Datasourcesandpopulation....................................................................................................78 4.3Poweranalyse..............................................................................................................................82 7| 4.4.Exposureandoutcomevariables.............................................................................................82 4.5Covariates.....................................................................................................................................88