{"paper_id":"469bd7be-b845-41ca-a0c5-afb563d167a2","body_text":"Chronic Hand Eczema is a Type 2 Disease: Evidences from Integrated Clinical Trial and Molecular Profiling | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Chronic Hand Eczema is a Type 2 Disease: Evidences from Integrated Clinical Trial and Molecular Profiling Marie Tauber, Perrine Gery, Aurélie Du-Thanh, Emilie Bérard, Fatma Jendoubi, and 20 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5537976/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background. Chronic hand eczema (CHE) is a debilitating skin condition characterized by pain, itch, and chronic inflammation, with a complex multifactorial origin. Its diverse presentations, including overlapping traits of atopic dermatitis, contact dermatitis, and psoriasis, make diagnosis and treatment particularly challenging. Despite being the most common occupational skin disease, the underlying immune mechanisms of CHE remain poorly understood. Methods. Here we conducted a comprehensive molecular profiling of CHE patients of all etiologies and morphologies and performed a phase 2b randomized, multicenter, double-blind, placebo-controlled clinical trial comparing dupilumab to placebo over 16 weeks. Results. We demonstrated that CHE is a type 2 immunity driven disease, regardless of etiological factors or clinical presentation. Transcriptomic profiles of CHE patients closely resemble those seen in both atopic dermatitis and psoriasis, with dysregulated genes affecting skin barrier function, leukocyte migration, cytotoxicity, and mixed type 1, 2, and 3 immunity. The clinical trial included 94 adults with moderate to severe CHE persisting for at least six months and resistant to potent topical corticosteroids. Compared to placebo control, 16-week dupilumab treatment significantly improved clinical severity and quality of life of CHE patients, while largely restoring appropriate transcriptomic and proteomic programs related to skin barrier and immune homeostasis. Conclusion. These findings demonstrate that IL-4Rα signaling is a critical regulator of CHE pathological features, independent of atopic dermatitis background or environmental triggers and support reclassifying CHE as a type 2 immune disorder, positioning dupilumab and IL-4/13 targeted therapies as leading treatments for moderate-to-severe patients. Biological sciences/Immunology/Translational immunology Health sciences/Diseases/Skin diseases Full Text Additional Declarations Yes there is potential Competing Interest. ADT : investigator, consultant or speaker for AbbVie, Sanofi, Pfizer, Leo Pharma et Lilly. NRP: arrangement fees from Sanofi AB: consultant for UCB, Janssen, Amgen, Abbvie, Novartis, Sanofi. FH: investigator, consultant or speaker for Sanofi, Leo Pharma, Galderma, Abbvie, Almirall MAL: investigator, consultant or speaker for Sanofi, Leo Pharma, Abbvie. AN: investigator, consultant or speaker for Pfizer, AbbVie, Eli Lilly, Galderma, Leo Pharma, Novartis, Sanofi, Incyte. JS: consultant, investigator for AbbVie, Almirall, Bristol Myers Squibb, Eli Lilly, Leo Pharma, Pfizer, Pierre Fabre, Sanofi. CP: investigator, consultant for Amgen, Abbvie, Bristol Myer Squibb, Boehringer, Celgene, Eli Lilly, Novartis, Janssen, Pierre Fabre, Pfizer, Leo Pharma. NG: consultant for Sanofi. MT: Investigator, consultant or speaker for Sanofi, Leo Pharma, Galderma, Abbvie, Almirall, Medac, Lilly, Pfizer. Supplementary Files StastisticalPlan.pdf Statistical Plan Analysis Clinicaltrialprotocol.pdf Clinical trial protocol NatCompaperTauberGaudenzioDupeczemainsupplementary.pdf Supplementary figures and tables Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-5537976\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":true,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":390225112,\"identity\":\"a94d76b4-ef26-4653-8150-f203b36ce509\",\"order_by\":0,\"name\":\"Marie Tauber\",\"email\":\"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIie3PvQrCMBDA8StZW1wFQZ9AOCmIg5JXsQi6VHTs7uBSnCu+RNwdUgJdrHQt2EEROhdcOnQw+LEIpqtD/pDABX4cAdDp/jT+vJvyFPh+8uoJPokRfEhcv+hFiPmZVaS7Pl15AVUHz6voPlxmtNE6jiE8/Cb9eIZhANhjWTTZuZg7282cAc8VhE9BmIAGS12buCjGGFuMFFxBkhxEBUhZuriTAQpKJQGuIqncIr/vyC2EAAqDmbUkh9BHe7LNItvwUTiB3MKVJJmSovTao815dYOyErThW/uLirzCr7kW6HQ6nU7dA5xjWRQ4Y//OAAAAAElFTkSuQmCC\",\"orcid\":\"https://orcid.org/0000-0001-6245-7442\",\"institution\":\"Centre International de Recherche en Infectiologie, University of Lyon 1 and ENS de Lyon, Inserm U1111 ; 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Inserm U1111\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Hugo\",\"middleName\":\"\",\"lastName\":\"Rimet\",\"suffix\":\"\"},{\"id\":390225120,\"identity\":\"3a8276f4-a6db-4494-8d88-524b999668ab\",\"order_by\":8,\"name\":\"Nadia Raison-Peyron\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, Saint-Eloi hospital, Montpellier University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Nadia\",\"middleName\":\"\",\"lastName\":\"Raison-Peyron\",\"suffix\":\"\"},{\"id\":390225121,\"identity\":\"b4f4976e-58b7-42c4-8503-3db5c77360b7\",\"order_by\":9,\"name\":\"Amel Bouznad\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, Larrey hospital, Toulouse University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Amel\",\"middleName\":\"\",\"lastName\":\"Bouznad\",\"suffix\":\"\"},{\"id\":390225122,\"identity\":\"d5841a1a-c941-43bf-b8af-53ebc2ad9e29\",\"order_by\":10,\"name\":\"Maria-Polina Konstantinou\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Dermatology, Larrey hospital, Toulouse University\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Maria-Polina\",\"middleName\":\"\",\"lastName\":\"Konstantinou\",\"suffix\":\"\"},{\"id\":390225123,\"identity\":\"8ce2651f-ee41-48c8-ae23-d955deaf31a4\",\"order_by\":11,\"name\":\"Jonathan Rioual\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Department of Clinical Epidemiology and Public Health, Toulouse university hospital\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Jonathan\",\"middleName\":\"\",\"lastName\":\"Rioual\",\"suffix\":\"\"},{\"id\":390225124,\"identity\":\"637baefc-fd66-43dd-bbcd-8fe5d9de52ed\",\"order_by\":12,\"name\":\"Lilian Basso\",\"email\":\"\",\"orcid\":\"https://orcid.org/0000-0002-2816-1557\",\"institution\":\"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), INSERM UMR1291, CNRS UMR5051, and University Toulouse III\",\"correspondingAuthor\":false,\"prefix\":\"\",\"firstName\":\"Lilian\",\"middleName\":\"\",\"lastName\":\"Basso\",\"suffix\":\"\"},{\"id\":390225125,\"identity\":\"525c7192-75de-4ec0-936a-03edc1da061b\",\"order_by\":13,\"name\":\"Juliette Mouiren\",\"email\":\"\",\"orcid\":\"\",\"institution\":\"Centre International de Recherche en Infectiologie, University of Lyon 1 and Ecole Normale Supérieure de Lyon; 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Sanofi, Incyte.\\r\\nJS: consultant, investigator for AbbVie, Almirall, Bristol Myers Squibb, Eli Lilly, Leo Pharma, Pfizer, Pierre Fabre, Sanofi.\\r\\nCP: investigator, consultant for Amgen, Abbvie, Bristol Myer Squibb, Boehringer, Celgene, Eli Lilly, Novartis, Janssen, Pierre Fabre, Pfizer, Leo Pharma.\\r\\nNG: consultant for Sanofi.\\r\\nMT: Investigator, consultant or speaker for Sanofi, Leo Pharma, Galderma, Abbvie, Almirall, Medac, Lilly, Pfizer.\",\"formattedTitle\":\"Chronic Hand Eczema is a Type 2 Disease: Evidences from Integrated Clinical Trial and Molecular Profiling\",\"fulltext\":[],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":false,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":true,\"hideJournal\":true,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":false,\"isAuthorSuppliedPdf\":true,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":true,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true},\"keywords\":\"\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-5537976/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-5537976/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eBackground.\\u003c/strong\\u003e Chronic hand eczema (CHE) is a debilitating skin condition characterized by pain, itch, and chronic inflammation, with a complex multifactorial origin. Its diverse presentations, including overlapping traits of atopic dermatitis, contact dermatitis, and psoriasis, make diagnosis and treatment particularly challenging. Despite being the most common occupational skin disease, the underlying immune mechanisms of CHE remain poorly understood. \\u003cstrong\\u003eMethods.\\u003c/strong\\u003e Here we conducted a comprehensive molecular profiling of CHE patients of all etiologies and morphologies and performed a phase 2b randomized, multicenter, double-blind, placebo-controlled clinical trial comparing dupilumab to placebo over 16 weeks.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults.\\u003c/strong\\u003e We demonstrated that CHE is a type 2 immunity driven disease, regardless of etiological factors or clinical presentation. Transcriptomic profiles of CHE patients closely resemble those seen in both atopic dermatitis and psoriasis, with dysregulated genes affecting skin barrier function, leukocyte migration, cytotoxicity, and mixed type 1, 2, and 3 immunity. The clinical trial included 94 adults with moderate to severe CHE persisting for at least six months and resistant to potent topical corticosteroids. Compared to placebo control, 16-week dupilumab treatment significantly improved clinical severity and quality of life of CHE patients, while largely restoring appropriate transcriptomic and proteomic programs related to skin barrier and immune homeostasis.\\u0026nbsp;\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion.\\u003c/strong\\u003e These findings demonstrate that IL-4Rα signaling is a critical regulator of CHE pathological features, independent of atopic dermatitis background or environmental triggers and support reclassifying CHE as a type 2 immune disorder, positioning dupilumab and IL-4/13 targeted therapies as leading treatments for moderate-to-severe patients.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Chronic Hand Eczema is a Type 2 Disease: Evidences from Integrated Clinical Trial and Molecular Profiling\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-12-17 12:39:56\",\"doi\":\"10.21203/rs.3.rs-5537976/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"researchsquare\",\"isNatureJournal\":false,\"hasQc\":true,\"allowDirectSubmit\":true,\"externalIdentity\":\"\",\"sideBox\":\"\",\"snPcode\":\"\",\"submissionUrl\":\"/submission\",\"title\":\"Research Square\",\"twitterHandle\":\"researchsquare\",\"acdcEnabled\":true,\"dfaEnabled\":false,\"editorialSystem\":\"\",\"reportingPortfolio\":\"\",\"inReviewEnabled\":false,\"inReviewRevisionsEnabled\":true}}],\"origin\":\"\",\"ownerIdentity\":\"22c7534c-d0bc-47c1-99c9-32403923fb23\",\"owner\":[],\"postedDate\":\"December 17th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"posted\",\"subjectAreas\":[{\"id\":41596852,\"name\":\"Biological sciences/Immunology/Translational immunology\"},{\"id\":41596853,\"name\":\"Health sciences/Diseases/Skin diseases\"}],\"tags\":[],\"updatedAt\":\"2025-09-24T14:41:23+00:00\",\"versionOfRecord\":[],\"versionCreatedAt\":\"2024-12-17 12:39:56\",\"video\":\"\",\"vorDoi\":\"\",\"vorDoiUrl\":\"\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-5537976\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-5537976\",\"identity\":\"rs-5537976\",\"version\":[\"v1\"]},\"buildId\":\"qtupq5eGEP_6zYnWcrvyt\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}