{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T03:01:20Z","timestamp":1789786880587,"version":"4.0.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/R513313\/1"],"award-info":[{"award-number":["EP\/R513313\/1"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,4,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Atopic dermatitis (AD) is characterized by skin barrier defects that are often measured by biophysical tools that observe the functional properties of the stratum corneum (SC).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To employ in vivo infrared spectroscopy alongside biophysical measurements to analyse changes in the chemical composition of the SC in relation to AD severity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted an observational cross-sectional cohort study where attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy measurements were collected on the forearm alongside surface pH, capacitance, erythema and transepidermal water loss (TEWL), combined with tape stripping, in a cohort of 75 participants (55 patients with AD stratified by phenotypic severity and 20 healthy controls). Common FLG variant alleles were genotyped.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Reduced hydration, elevated TEWL and redness were all associated with greater AD severity. Spectral analysis showed a reduction in 1465\u2005cm\u20131 (full width half maximum) and 1340\u2005cm\u20131 peak areas, indicative of less orthorhombic lipid ordering and reduced carboxylate functional groups, which correlated with clinical severity (lipid structure r = \u20130.59, carboxylate peak area r = \u20130.50).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>ATR-FTIR spectroscopy is a suitable tool for the characterization of structural skin barrier defects in AD and has potential as a clinical tool for directing individual treatment based on chemical structural deficiencies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ced\/llad416","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T23:21:37Z","timestamp":1701127297000},"page":"466-477","source":"Crossref","is-referenced-by-count":7,"title":["Characterization of skin barrier defects using infrared spectroscopy in patients with atopic dermatitis"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1296-0098","authenticated-orcid":false,"given":"Samuel F","family":"Williams","sequence":"first","affiliation":[{"name":"Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School , Sheffield , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Wan","sequence":"additional","affiliation":[{"name":"Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School , Sheffield , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1595-7441","authenticated-orcid":false,"given":"John","family":"Chittock","sequence":"additional","affiliation":[{"name":"Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School , Sheffield , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Brown","sequence":"additional","affiliation":[{"name":"Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School , Sheffield , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Wigley","sequence":"additional","affiliation":[{"name":"Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School , Sheffield , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4428-2428","authenticated-orcid":false,"given":"Michael\u00a0J","family":"Cork","sequence":"additional","affiliation":[{"name":"Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School , Sheffield , UK"},{"name":"Sheffield Children\u2019s NHS Foundation Trust, Sheffield Children\u2019s Hospital , Western Bank, Sheffield , UK"},{"name":"Sheffield Teaching Hospitals NHS Foundation Trust, The Royal Hallamshire Hospital , Sheffield , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7363-140X","authenticated-orcid":false,"given":"Simon G","family":"Danby","sequence":"additional","affiliation":[{"name":"Sheffield Dermatology Research, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield Medical School , Sheffield , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"2024042316201673400_llad416-B1","doi-asserted-by":"crossref","first-page":"207","DOI":"10.4168\/aair.2018.10.3.207","article-title":"Significance of skin barrier dysfunction in atopic dermatitis","volume":"10","author":"Kim","year":"2018","journal-title":"Allergy Asthma Immunol Res"},{"key":"2024042316201673400_llad416-B2","first-page":"16","article-title":"Atopic dermatitis and the stratum corneum: part 1: the role of filaggrin in the stratum corneum barrier and atopic skin","volume":"6","author":"Levin","year":"2013","journal-title":"J Clin Aesthet Dermatol"},{"key":"2024042316201673400_llad416-B3","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1111\/jdv.17787","article-title":"Natural moisturizing factors in children with and without eczema: associations with lifestyle and genetic factors","volume":"36","author":"Basu","year":"2022","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2024042316201673400_llad416-B4","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/j.1398-9995.2010.02540.x","article-title":"Levels of filaggrin degradation products are influenced by both filaggrin genotype and atopic dermatitis severity","volume":"66","author":"Kezic","year":"2011","journal-title":"Allergy"},{"key":"2024042316201673400_llad416-B5","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.anai.2019.03.033","article-title":"Early immunologic changes during the onset of atopic dermatitis","volume":"123","author":"Brunner","year":"2019","journal-title":"Ann Allergy Asthma Immunol"},{"key":"2024042316201673400_llad416-B6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/j.1467-2494.2007.00386.x","article-title":"Profiling of serine protease activities in human stratum corneum and detection of a stratum corneum tryptase-like enzyme","volume":"29","author":"Voegeli","year":"2007","journal-title":"Int J Cosmet Sci"},{"key":"2024042316201673400_llad416-B7","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1016\/j.bbamem.2008.01.022","article-title":"Molecular organization of the lipid matrix in intact stratum corneum using ATR-FTIR spectroscopy","volume":"1778","author":"Boncheva","year":"2008","journal-title":"Biochim Biophys Acta"},{"key":"2024042316201673400_llad416-B8","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1111\/j.1600-0625.2009.00868.x","article-title":"Depth profiling of stratum corneum hydration in vivo: a comparison between conductance and confocal raman spectroscopic measurements","volume":"18","author":"Boncheva","year":"2009","journal-title":"Exp Dermatol"},{"key":"2024042316201673400_llad416-B9","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.ejpb.2008.02.002","article-title":"The determination of stratum corneum thicknes: an alternative approach","volume":"69","author":"Russell","year":"2008","journal-title":"Eur J Pharm Biopharm"},{"key":"2024042316201673400_llad416-B10","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1007\/s13555-020-00426-3","article-title":"An investigation of the skin barrier restoring effects of a cream and lotion containing ceramides in a multi-vesicular emulsion in people with dry, eczema-prone, skin: the RESTORE study phase 1","volume":"10","author":"Danby","year":"2020","journal-title":"Dermatol Ther (Heidelb)"},{"key":"2024042316201673400_llad416-B11","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1111\/j.0022-202X.2004.22317.x","article-title":"Relationship between NMF (lactate and potassium) content and the physical properties of the stratum corneum in healthy subjects","volume":"122","author":"Nakagawa","year":"2004","journal-title":"J Invest Dermatol"},{"key":"2024042316201673400_llad416-B12","author":"NHS Digital"},{"key":"2024042316201673400_llad416-B13","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1111\/j.1600-0625.2011.01259.x","article-title":"Distinct barrier integrity phenotypes in filaggrin-related atopic eczema following sequential tape stripping and lipid profiling","volume":"20","author":"Angelova-Fischer","year":"2011","journal-title":"Exp Dermatol"},{"key":"2024042316201673400_llad416-B14","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1111\/j.1365-2133.2010.10068.x","article-title":"Filaggrin loss-of-function mutations are associated with early-onset eczema, eczema severity and transepidermal water loss at 3\u2005months of age","volume":"163","author":"Flohr","year":"2010","journal-title":"Br J Dermatol"},{"key":"2024042316201673400_llad416-B15","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1194\/jlr.P030338","article-title":"Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients","volume":"53","author":"Janssens","year":"2012","journal-title":"J Lipid Res"},{"key":"2024042316201673400_llad416-B16","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1016\/j.bbagen.2007.06.014","article-title":"Physical characterization of the stratum corneum of an in vitro psoriatic skin model by ATR-FTIR and Raman spectroscopies","author":"Bernard","year":"2007","journal-title":"Biochim Biophys Acta"},{"key":"2024042316201673400_llad416-B17","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S1388-1981(99)00086-4","article-title":"Physical characterization of the stratum corneum of an in vitro human skin equivalent produced by tissue engineering and its comparison with normal human skin by ATR-FTIR spectroscopy and thermal analysis (DSC)","author":"Pouliot","year":"1999","journal-title":"Biochim Biophys Acta"},{"key":"2024042316201673400_llad416-B18","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1111\/exd.12293","article-title":"The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients","volume":"23","author":"van Smeden","year":"2014","journal-title":"Exp Dermatol"},{"key":"2024042316201673400_llad416-B19","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/j.bbamem.2006.04.009","article-title":"Determination of molecular conformation and permeation in skin via IR spectroscopy, microscopy, and imaging","author":"Mendelsohn","year":"2006","journal-title":"Biochim Biophys Acta"},{"key":"2024042316201673400_llad416-B20","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/bjd.12908","article-title":"Lipid to protein ratio plays an important role in the skin barrier function in patients with atopic eczema","volume":"170","author":"Janssens","year":"2014","journal-title":"Br J Dermatol"},{"key":"2024042316201673400_llad416-B21","doi-asserted-by":"crossref","first-page":"1754706","DOI":"10.1080\/21688370.2020.1754706","article-title":"Lipid depletion enables permeation of Staphylococcus aureus bacteria through human stratum corneum","volume":"8","author":"Lipsky","year":"2020","journal-title":"Tissue Barriers"},{"key":"2024042316201673400_llad416-B22","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1038\/jid.2010.161","article-title":"Changes in the ceramide profile of atopic dermatitis patients","volume":"130","author":"Ishikawa","year":"2010","journal-title":"J Invest Dermatol"},{"key":"2024042316201673400_llad416-B23","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1111\/bjd.20955","article-title":"Enhancement of stratum corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema-prone skin","volume":"186","author":"Danby","year":"2022","journal-title":"Br J Dermatol"},{"key":"2024042316201673400_llad416-B24","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/j.1398-9995.2010.02326.x","article-title":"Stratum corneum lipids, skin barrier function and filaggrin mutations in patients with atopic eczema","volume":"65","author":"Jungersted","year":"2010","journal-title":"Allergy"},{"key":"2024042316201673400_llad416-B25","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1117\/1.429890","article-title":"Band analysis of hydrated human skin stratum corneum attenuated total reflectance Fourier transform infrared spectra in vivo","volume":"3","author":"Lucassen","year":"1998","journal-title":"J Biomed Opt"},{"key":"2024042316201673400_llad416-B26","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1038\/ng1767","article-title":"Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis","volume":"38","author":"Palmer","year":"2006","journal-title":"Nat Genet"},{"key":"2024042316201673400_llad416-B27","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1038\/sj.jid.5700587","article-title":"Null mutations in the filaggrin gene (FLG) determine major susceptibility to early-onset atopic dermatitis that persists into adulthood","volume":"127","author":"Barker","year":"2007","journal-title":"J Invest Dermatol"},{"key":"2024042316201673400_llad416-B28","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1111\/j.1365-2133.2006.07500.x","article-title":"Filaggrin loss-of-function variant contributes to atopic dermatitis risk in the population of Northern Germany","volume":"155","author":"Ruether","year":"2006","journal-title":"Br J Dermatol"},{"key":"2024042316201673400_llad416-B29","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1111\/jdv.12753","article-title":"Profile of skin barrier proteins (filaggrin, claudins 1 and 4) and Th1\/Th2\/Th17 cytokines in adults with atopic dermatitis","volume":"29","author":"Batista","year":"2015","journal-title":"J Eur Acad Dermatol Venereol"},{"key":"2024042316201673400_llad416-B30","doi-asserted-by":"crossref","first-page":"640","DOI":"10.2340\/00015555-1815","article-title":"Skin barrier integrity and natural moisturising factor levels after cumulative dermal exposure to alkaline agents in atopic dermatitis","volume":"94","author":"Angelova-Fischer","year":"2014","journal-title":"Acta Derm Venereol"},{"key":"2024042316201673400_llad416-B31","doi-asserted-by":"crossref","first-page":"326","DOI":"10.12968\/npre.2015.13.7.326","article-title":"Prescribing for children with atopic eczema in primary care","volume":"13","author":"Penzer","year":"2015","journal-title":"Nurse Prescribing"},{"key":"2024042316201673400_llad416-B32","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1001\/archderm.1991.04520010052006","article-title":"Skin aging: effect on trans\u00adepidermal water loss, stratum corneum hydration, skin surface pH, and casual sebum content","volume":"127","author":"Wilhelm","year":"1991","journal-title":"Arch Dermatol"},{"key":"2024042316201673400_llad416-B33","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jaci.2016.03.031","article-title":"Association between domestic water hardness, chlorine, and atopic dermatitis risk in early life: a population-based cross-sectional study","volume":"138","author":"Perkin","year":"2016","journal-title":"J Allergy Clin Immunol"},{"key":"2024042316201673400_llad416-B34","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jaci.2007.12.1161","article-title":"Intrinsically defective skin barrier function in children with atopic dermatitis correlates with disease severity","volume":"121","author":"Gupta","year":"2008","journal-title":"J Allergy Clin Immunol"},{"key":"2024042316201673400_llad416-B35","doi-asserted-by":"crossref","DOI":"10.1001\/jamadermatol.2019.1946","article-title":"Association of filaggrin loss-of-function variants with race in children with atopic dermatitis","volume":"155","author":"Margolis","year":"2019","journal-title":"JAMA Dermatol"}],"container-title":["Clinical and Experimental Dermatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ced\/advance-article-pdf\/doi\/10.1093\/ced\/llad416\/56587273\/llad416.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ced\/article-pdf\/49\/5\/466\/57305926\/llad416.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ced\/article-pdf\/49\/5\/466\/57305926\/llad416.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,4,23]],"date-time":"2024-04-23T17:29:38Z","timestamp":1713893378000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ced\/article\/49\/5\/466\/7451571"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":35,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,11,27]]},"published-print":{"date-parts":[[2024,4,23]]}},"URL":"https:\/\/doi.org\/10.1093\/ced\/llad416","relation":{},"ISSN":["0307-6938","1365-2230"],"issn-type":[{"value":"0307-6938","type":"print"},{"value":"1365-2230","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,5]]},"published":{"date-parts":[[2023,11,27]]}}}