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Stratum Corneum Ceramide Profiles Provide Reliable Indicators of Remission and Potential Flares in Atopic Dermatitis

      Atopic dermatitis (AD) is a chronic inflammatory skin disease. Prevention of exacerbation of AD is a crucial issue for all physicians. However, exacerbation of AD often is seen during reduction of AD treatment, even with appropriate follow-up by tapered topical corticosteroids and daily topical moisturizers, indicating the need for good indicators of AD remission. We hypothesized that the presence of mutations in FLG or the stratum corneum ceramide profile on AD remission phase may predict the ease of AD exacerbation. This study examined the differences in the frequency of FLG mutations or stratum corneum ceramide profiles (stratum corneum levels and carbon chain length for 11 ceramide classes [ceramides containing nonhydroxy fatty acids and dihydrosphingosines; nonhydroxy fatty acids and sphingosines; nonhydroxy fatty acids and 6-hydroxysphingosines; nonhydroxy fatty acids and phytosphingosines; a-hydroxy fatty acids and dihydrosphingosines; a-hydroxy fatty acids and sphingosines; a-hydroxy fatty acids and 6-hydroxysphingosines; a-hydroxy fatty acids and phytosphingosines; ester-linked fatty acids, o-hydroxy fatty acids, and sphingosines; ester-linked fatty acids, o-hydroxy fatty acids, and 6-hydroxysphingosines; and ester-linked fatty acids, o-hydroxy fatty acids, and phytosphingosines]) at AD remission phase between the two AD study groups: subsequent exacerbation (‒) and (+) of AD. The frequency of FLG mutations did not differ between the study groups. On the other hand, the carbon chain lengths of ceramides containing nonhydroxy fatty acids and dihydrosphingosines, nonhydroxy fatty acids and sphingosines, and nonhydroxy fatty acids and 6-hydroxysphingosines were shorter in the exacerbated AD group than in the maintained-AD group. Thus, the stratum corneum ceramide profile at the remission phase of AD is a potential biomarker, predicting the likelihood of substantial AD remission or subsequent AD exacerbation.

      Abbreviations:

      AD (atopic dermatitis), AH (ceramides containing a-hydroxy fatty acids and 6-hydroxysphingosines), NDS (ceramides containing nonhydroxy fatty acids and dihydrosphingosines), NH (ceramides containing nonhydroxy fatty acids and 6-hydroxysphingosines), NP (ceramides containing nonhydroxy fatty acids and phytosphingosines), NS (ceramides containing nonhydroxy fatty acids and sphingosines), SC (stratum corneum), TARC (thymus and activation regulated chemokine)
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      References

        • Akiyama M.
        FLG mutations in ichthyosis vulgaris and atopic eczema: spectrum of mutations and population genetics.
        Br J Dermatol. 2010; 162: 472-477
        • Drislane C.
        • Irvine A.D.
        The role of filaggrin in atopic dermatitis and allergic disease.
        Ann Allergy Asthma Immunol. 2020; 124: 36-43
        • Eichenfield L.F.
        • Tom W.L.
        • Berger T.G.
        • Krol A.
        • Paller A.S.
        • Schwarzenberger K.
        • et al.
        Guidelines of care for the management of atopic dermatitis: section 2. Management and treatment of atopic dermatitis with topical therapies.
        J Am Acad Dermatol. 2014; 71: 116-132
        • Elias P.M.
        • Hatano Y.
        • Williams M.L.
        Basis for the barrier abnormality in atopic dermatitis: outside-inside-outside pathogenic mechanisms.
        J Allergy Clin Immunol. 2008; 121: 1337-1343
        • Elias P.M.
        • Wakefield J.S.
        Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis.
        J Allergy Clin Immunol. 2014; 134: 781-791.e1
        • Henderson J.
        • Northstone K.
        • Lee S.P.
        • Liao H.
        • Zhao Y.
        • Pembrey M.
        • et al.
        The burden of disease associated with filaggrin mutations: a population-based, longitudinal birth cohort study.
        J Allergy Clin Immunol. 2008; 121: 872-877.e9
        • Irvine A.D.
        • McLean W.H.
        • Leung D.Y.
        Filaggrin mutations associated with skin and allergic diseases.
        N Engl J Med. 2011; 365: 1315-1327
        • Ishikawa J.
        • Narita H.
        • Kondo N.
        • Hotta M.
        • Takagi Y.
        • Masukawa Y.
        • et al.
        Changes in the ceramide profile of atopic dermatitis patients.
        J Invest Dermatol. 2010; 130: 2511-2514
        • Kataoka Y.
        Thymus and activation-regulated chemokine as a clinical biomarker in atopic dermatitis.
        J Dermatol. 2014; 41: 221-229
        • Katoh N.
        • Ohya Y.
        • Ikeda M.
        • Ebihara T.
        • Katayama I.
        • Saeki H.
        • et al.
        Japanese guidelines for atopic dermatitis 2020.
        Allergol Int. 2020; 69: 356-369
        • Kono M.
        • Nomura T.
        • Ohguchi Y.
        • Mizuno O.
        • Suzuki S.
        • Tsujiuchi H.
        • et al.
        Comprehensive screening for a complete set of Japanese-population-specific filaggrin gene mutations.
        Allergy. 2014; 69: 537-540
        • Leung D.Y.M.
        • Berdyshev E.
        • Goleva E.
        Cutaneous barrier dysfunction in allergic diseases.
        J Allergy Clin Immunol. 2020; 145 ([published correction appears in J Allergy Clin Immunol 2021;148:905]): 1485-1497
        • Masukawa Y.
        • Narita H.
        • Shimizu E.
        • Kondo N.
        • Sugai Y.
        • Oba T.
        • et al.
        Characterization of overall ceramide species in human stratum corneum.
        J Lipid Res. 2008; 49: 1466-1476
        • Nemoto-Hasebe I.
        • Akiyama M.
        • Nomura T.
        • Sandilands A.
        • McLean W.H.
        • Shimizu H.
        FLG mutation p.Lys4021X in the C-terminal imperfect filaggrin repeat in Japanese patients with atopic eczema.
        Br J Dermatol. 2009; 161: 1387-1390
        • Nomura T.
        • Sandilands A.
        • Akiyama M.
        • Liao H.
        • Evans A.T.
        • Sakai K.
        • et al.
        Unique mutations in the filaggrin gene in Japanese patients with ichthyosis vulgaris and atopic dermatitis.
        J Allergy Clin Immunol. 2007; 119: 434-440
        • O'Regan G.M.
        • Kemperman P.M.
        • Sandilands A.
        • Chen H.
        • Campbell L.E.
        • Kroboth K.
        • et al.
        Raman profiles of the stratum corneum define 3 filaggrin genotype-determined atopic dermatitis endophenotypes.
        J Allergy Clin Immunol. 2010; 126: 574-580.e1
        • Riethmuller C.
        • McAleer M.A.
        • Koppes S.A.
        • Abdayem R.
        • Franz J.
        • Haftek M.
        • et al.
        Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis.
        J Allergy Clin Immunol. 2015; 136: 1573-1580.e2
        • Saeki H.
        • Furue M.
        • Furukawa F.
        • Hide M.
        • Ohtsuki M.
        • Katayama I.
        • et al.
        Guidelines for management of atopic dermatitis.
        J Dermatol. 2009; 36: 563-577
        • Sandilands A.
        • O'Regan G.M.
        • Liao H.
        • Zhao Y.
        • Terron-Kwiatkowski A.
        • Watson R.M.
        • et al.
        Prevalent and rare mutations in the gene encoding filaggrin cause ichthyosis vulgaris and predispose individuals to atopic dermatitis.
        J Invest Dermatol. 2006; 126: 1770-1775
        • Sandilands A.
        • Sutherland C.
        • Irvine A.D.
        • McLean W.H.
        Filaggrin in the frontline: role in skin barrier function and disease.
        J Cell Sci. 2009; 122: 1285-1294
        • Sasaki T.
        • Furusyo N.
        • Shiohama A.
        • Takeuchi S.
        • Nakahara T.
        • Uchi H.
        • et al.
        Filaggrin loss-of-function mutations are not a predisposing factor for atopic dermatitis in an Ishigaki Island under subtropical climate.
        J Dermatol Sci. 2014; 76: 10-15
        • Sugiura A.
        • Nomura T.
        • Mizuno A.
        • Imokawa G.
        Reevaluation of the non-lesional dry skin in atopic dermatitis by acute barrier disruption: an abnormal permeability barrier homeostasis with defective processing to generate ceramide.
        Arch Dermatol Res. 2014; 306: 427-440
        • Takeichi T.
        • Okuno Y.
        • Kawamoto A.
        • Inoue T.
        • Nagamoto E.
        • Murase C.
        • et al.
        Reduction of stratum corneum ceramides in Neu-Laxova syndrome caused by phosphoglycerate dehydrogenase deficiency.
        J Lipid Res. 2018; 59: 2413-2420
        • Teye K.
        • Numata S.
        • Krol R.P.
        • Ishii N.
        • Matsuda M.
        • Lee J.B.
        • et al.
        Prevalence of filaggrin gene mutations in patients with atopic dermatitis and ichthyosis vulgaris in Kyushu area of Japan and South Korea.
        J Dermatol Sci. 2017; 86: 174-177
        • Weidinger S.
        • Beck L.A.
        • Bieber T.
        • Kabashima K.
        • Irvine A.D.
        Atopic dermatitis.
        Nat Rev Dis Primers. 2018; 4: 1
        • Weidinger S.
        • O'Sullivan M.
        • Illig T.
        • Baurecht H.
        • Depner M.
        • Rodriguez E.
        • et al.
        Filaggrin mutations, atopic eczema, hay fever, and asthma in children.
        J Allergy Clin Immunol. 2008; 121: 1203-1209.e1
        • Wollenberg A.
        • Barbarot S.
        • Bieber T.
        • Christen-Zaech S.
        • Deleuran M.
        • Fink-Wagner A.
        • et al.
        Consensus-based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part I [published correction appears in J Eur Acad Dermatol Venereol 2019;33:1436].
        J Eur Acad Dermatol Venereol. 2018; 32: 657-682
        • Yokose U.
        • Ishikawa J.
        • Morokuma Y.
        • Naoe A.
        • Inoue Y.
        • Yasuda Y.
        • et al.
        The ceramide [NP]/[NS] ratio in the stratum corneum is a potential marker for skin properties and epidermal differentiation.
        BMC Dermatol. 2020; 20: 6