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Effect of moisturizers on epidermal barrier function

      Abstract

      A daily moisturizing routine is a vital part of the management of patients with atopic dermatitis and other dry skin conditions. The composition of the moisturizer determines whether the treatment strengthens or deteriorates the skin barrier function, which may have consequences for the outcome of the dermatitis. One might expect that a patient's impaired skin barrier function should improve in association with a reduction in the clinical signs of dryness. Despite visible relief of the dryness symptoms, however, the abnormal transepidermal water loss has been reported to remain high, or even to increase under certain regimens, whereas other moisturizers improve skin barrier function. Differing outcomes have also been reported in healthy skin: some moisturizers produce deterioration in skin barrier function and others improve the skin. Possible targets for barrier-influencing moisturizing creams include the intercellular lipid bilayers, where the fraction of lipids forming a fluid phase might be changed due to compositional or organizational changes. Other targets are the projected size of the corneocytes or the thickness of the stratum corneum. Moisturizers with barrier-improving properties may delay relapse of dermatitis in patients with atopic dermatitis. In a worst-case scenario, treatment with moisturizing creams could increase the risks of dermatitis and asthma.
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      References

        • Holden C.
        • English J.
        • Hoare C.
        • et al.
        Advised best practice for the use of emollients in eczema and other dry skin conditions.
        J Dermatol Treat. 2002; 13: 103-106
        • Buraczewska I.
        • Berne B.
        • Lindberg M.
        • Torma H.
        • Loden M.
        Changes in skin barrier function following long-term treatment with moisturizers, a randomized controlled trial.
        Br J Dermatol. 2007; 156: 492-498
        • Held E.
        • Sveinsdottir S.
        • Agner T.
        Effect of long-term use of moisturizers on skin hydration, barrier function and susceptibility to irritants.
        Acta Derm Venereol (Stockh). 1999; 79: 49-51
        • Zachariae C.
        • Held E.
        • Johansen J.D.
        • Menne T.
        • Agner T.
        Effect of a moisturizer on skin susceptibility to NiCl2.
        Acta Derm Venereol. 2003; 83: 93-97
        • Vilaplana J.
        • Coll J.
        • Trullás C.
        • Axón A.
        • Pelejero C.
        Clinical and non-invasive evaluation of 12% ammonium lactate emulsion for the treatment of dry skin in atopic and non-atopic subjects.
        Acta Derm Venereol (Stockh). 1992; 72: 28-33
        • Hoare C.
        • Li Wan Po A.
        • Williams H.
        Systematic review of treatments for atopic eczema.
        Health Technol Assess. 2000; 4: 1-191
        • Elias P.M.
        • Wood L.C.
        • Feingold K.R.
        Epidermal pathogenesis of inflammatory dermatoses.
        Am J Contact Dermat. 1999; 10: 119-126
        • Palmer C.N.
        • Irvine A.D.
        • Terron-Kwiatkowski A.
        • et al.
        Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis.
        Nat Genet. 2006; 38: 441-446
        • Weidinger S.
        • Illig T.
        • Baurecht H.
        • et al.
        Loss-of-function variations within the filaggrin gene predispose for atopic dermatitis with allergic sensitizations.
        J Allergy Clin Immunol. 2006; 118: 214-219
        • Rawlings A.V.
        • Harding C.R.
        Moisturization and skin barrier function.
        Dermatol Ther. 2004; 17: 43-48
        • Candi E.
        • Schmidt R.
        • Melino G.
        The cornified envelope: a model of cell death in the skin.
        Nat Rev Mol Cell Biol. 2005; 6: 328-340
        • Ginger R.S.
        • Blachford S.
        • Rowland J.
        • Rowson M.
        • Harding C.R.
        Filaggrin repeat number polymorphism is associated with a dry skin phenotype.
        Arch Dermatol Res. 2005; 297: 235-241
        • Loden M.
        • Buraczewska I.
        • Halvarsson K.
        Facial anti-wrinkle cream: influence of product presentation on effectiveness: a randomized and controlled study.
        Skin Res Technol. 2007; 13: 189-194
        • Lynfield Y.L.
        • Schechter B.A.
        Choosing and using a vehicle.
        J Am Acad Dermatol. 1984; 10: 56-59
        • Schlagel C.A.
        • Sanborn E.C.
        The weights of topical preparations required for total and partial body inunction.
        J Invest Dermatol. 1964; 42: 253-256
        • Ivens U.I.
        • Steinkjer B.
        • Serup J.
        • Tetens V.
        Ointment is evenly spread on the skin, in contrast to creams and solutions.
        Br J Dermatol. 2001; 145: 264-267
        • Rhodes L.E.
        • Diffey B.L.
        Fluorescence spectroscopy: a rapid, noninvasive method for measurement of skin surface thickness of topical agents.
        Br J Dermatol. 1997; 136: 12-17
        • Johnson R.
        • Nusbaum B.P.
        • Horwitz S.N.
        • Frost P.
        Transfer of topically applied tetracycline in various vehicles.
        Arch Dermatol. 1983; 119: 660-663
        • Lodén M.
        • Olsson H.
        • Skare L.
        • Axéll T.
        Instrumental and sensory evaluation of the frictional response of the skin following a single application of five moisturizing creams.
        J Soc Cosmet Chem. 1992; 43: 13-20
        • Nicholls S.
        • King C.S.
        • Marks R.
        Short term effects of emollients and a bath oil on the stratum corneum.
        J Soc Cosmet Chem. 1978; 29: 617-624
        • Garber C.A.
        • Nightingale C.T.
        Characterizing cosmetic effects and skin morphology by scanning electron microscopy.
        J Soc Cosmet Chem. 1976; 27: 509-531
        • Mignot J.
        • Zahouani H.
        • Rondot D.
        • Nardin P.
        Morphological study of human skin relief.
        Bioeng Skin. 1987; 3: 177-196
        • Lodén M.
        • Lindberg M.
        The influence of a single application of different moisturizers on the skin capacitance.
        Acta Derm Venereol. 1991; 71: 79-82
        • Lodén M.
        The increase in skin hydration after application of emollients with different amounts of lipids.
        Acta Derm Venereol. 1992; 72: 327-330
        • Buraczewska I.
        • Brostrom U.
        • Loden M.
        Artificial reduction in transepidermal water loss improves skin barrier function.
        Br J Dermatol. 2007; 157: 82-86
        • Wertz P.W.
        • Downing D.T.
        Metabolism of topically applied fatty acid methyl esters in BALB/C mouse epidermis.
        J Dermatol Sci. 1990; 1: 33-38
        • Moloney S.J.
        The in-vitro percutaneous absorption of glycerol trioleate through hairless mouse skin.
        J Pharm Pharmacol. 1988; 40: 819-821
        • Rawlings A.V.
        • Scott I.R.
        • Harding C.R.
        • Bowser P.A.
        Stratum corneum moisturization at the molecular level.
        J Invest Dermatol. 1995; 103: 731-740
        • Escobar S.O.
        • Achenbach R.
        • Innantuono R.
        • Torem V.
        Topical fish oil in psoriasis—a controlled and blind study.
        Clin Exp Dermatol. 1992; 17: 159-162
        • Tollesson A.
        • Frithz A.
        Borage oil, an effective new treatment for infantile seborrhoeic dermatitis.
        Br J Dermatol. 1993; 129: 95
        • Feingold K.R.
        • Brown B.E.
        • Lear S.R.
        • Moser A.H.
        • Elias P.M.
        Effect of essential fatty acid deficiency on cutaneous sterol synthesis.
        J Invest Dermatol. 1986; 87: 588-591
        • Imokawa G.
        • Akasaki S.
        • Hattori M.
        • Yoshizuka N.
        Selective recovery of deranged water-holding properties by stratum corneum lipids.
        J Invest Dermatol. 1986; 87: 758-761
        • Man M.Q.
        • Feingold K.R.
        • Elias P.M.
        Exogenous lipids influence permeability barrier recovery in acetone-treated murine skin.
        Arch Dermatol. 1993; 129: 728-738
        • Oudshoorn M.H.
        • Rissmann R.
        • van der Coelen D.
        • Hennink W.E.
        • Ponec M.
        • Bouwstra J.A.
        Effect of synthetic vernix biofilms on barrier recovery of damaged mouse skin.
        Exp Dermatol. 2009; 18: 695-703
        • Middleton J.
        Development of a skin cream designed to reduce dry and flaky skin.
        J Soc Cosmet Chem. 1974; 25: 519-534
        • Sahlin A.
        • Edlund F.
        • Lodén M.A.
        A double-blind and controlled study on the influence of the vehicle on the skin susceptibility to stinging from lactic acid.
        Int J Cosmet Sci. 2007; 29: 385-390
        • Lalor C.B.
        • Flynn G.L.
        • Weiner N.
        Formulation factors affecting release of drug from topical formulations. 1. Effect of emulsion type upon in vitro delivery of ethyl p-aminobenzoate.
        J Pharm Sci. 1994; 83: 1525-1528
        • Wiren K.
        • Frithiof H.
        • Sjöqvist C.
        • Loden M.
        Enhancement of bioavailability by lowering of fat content in topical formulations.
        Br J Dermatol. 2008; 160: 552-556
        • Smith E.W.
        • Meyer E.
        • Haigh J.M.
        Blanching activities of betamethasone formulations. The effect of dosage form on topical drug availability.
        Arzneimittelforschung. 1990; 40: 618-621
        • Denda M.
        • Koyama J.
        • Namba R.
        • Horii I.
        Stratum corneum lipid morphology and transepidermal water loss in normal skin and surfactant-induced scaly skin.
        Arch Dermatol Res. 1994; 286: 41-46
        • Thune P.
        Evaluation of the hydration and the water-holding capacity in atopic skin and so-called dry skin.
        Acta Derm Venereol Suppl (Stockh). 1989; 144: 133-135
        • Lodén M.
        • Olsson H.
        • Axell T.
        • Linde Y.W.
        Friction, capacitance and transepidermal water loss (TEWL) in dry atopic and normal skin.
        Br J Dermatol. 1992; 126: 137-141
        • Werner Y.
        • Lindberg M.
        Transepidermal water loss in dry and clinically normal skin in patients with atopic dermatitis.
        Acta Derm Venereol. 1985; 65: 102-105
        • Serup J.
        • Blichmann C.W.
        Epidermal hydration of psoriasis plaques and the relation to scaling. Measurement of electrical conductance and transepidermal water loss.
        Acta Derm Venereol (Stockh). 1987; 67: 357-359
        • Motta S.
        • Monti M.
        • Sesana S.
        • Mellesi L.
        • Ghidoni R.
        • Caputo R.
        Abnormality of water barrier function in psoriasis.
        Arch Dermatol. 1994; 130: 452-456
        • Ghadially R.
        • Reed J.T.
        • Elias P.M.
        Stratum corneum structure and function correlates with phenotype in psoriasis.
        J Invest Dermatol. 1996; 107: 558-564
        • Blank I.H.
        Factors which influence the water content of the stratum corneum.
        J Invest Dermatol. 1952; 18: 433-440
        • Blank I.H.
        Further observations on factors which influence the water content of the stratum corneum.
        J Invest Dermatol. 1953; 21: 259-271
        • Grove G.L.
        • Kligman A.M.
        Corneocytes size as an indirect measure of epidermal proliferative activity.
        in: Marks R. Plewig G. Stratum corneum. Springer-Verlag, New York1983: 191-194
        • Rougier A.
        • Lotte C.
        • Corcuff P.
        • Maibach H.I.
        Relationship between skin permeability and corneocyte size according to anatomic site, age, and sex in man.
        J Soc Cosmet Chem. 1988; 39: 15-26
        • Potts R.O.
        • Francoeur M.L.
        The influence of stratum corneum morphology on water permeability.
        J Invest Dermatol. 1991; 96: 495-499
        • Imokawa G.
        • Akasaki S.
        • Minematsu Y.
        • Kawai M.
        Importance of intercellular lipids in water-retention properties of the stratum corneum: induction and recovery study of surfactant dry skin.
        Arch Dermatol Res. 1989; 281: 45-51
        • Leveque J.L.
        • Grove G.L.
        • de Rigal J.
        • Corcuff P.
        • Kligman A.M.
        Biophysical characterization of dry facial skin.
        J Soc Cosmet Chem. 1987; 82: 171-177
        • Wehr R.
        • Krochmal L.
        • Raqsdale F. Bagatell. W.
        A controlled two-center study of lactate 12% lotion and a petrolatum-based creme in patients with xerosis.
        Cutis. 1986; 37: 205-209
        • Rogers R.S.
        • Callen J.
        • Wehr R.
        • Krochmal L.
        Comparative efficacy of 12% ammonium lactate lotion and 5% lactic acid lotion in the treatment of moderate to severe xerosis.
        J Am Acad Dermatol. 1989; 21: 714-716
        • Siskin S.B.
        • Quinlan P.J.
        • Finkelstein M.S.
        • Marlucci M.
        • Maglietta T.G.
        • Gibson J.R.
        The effect of ammonium lactate 12% lotion versus no therapy in the treatment of dry skin of the heels.
        Int J Dermatol. 1983; 32: 905-907
        • Dahl M.V.
        • Dahl A.C.
        12% lactate lotion for the treatment of xerosis.
        Arch Dermatol. 1983; 119: 27-30
        • Wehr R.F.
        • Kantor I.
        • Jones E.L.
        • McPhee M.E.
        A controlled comparative efficacy study of 5% ammonium lactate lotion versus an emollient control lotion in the treatment of moderate xerosis.
        J Am Acad Dermatol. 1991; 25: 849-851
        • Middleton J.D.
        • Roberts M.E.
        Effect of a skin cream containing the sodium salt of pyrrolidone carboxylic acid on dry and flaky skin.
        J Soc Cosmet Chem. 1978; 29: 201-205
        • Schölermann A.
        • Banké-Bochita J.
        • Bohnsack K.
        • Rippke F.
        • Herrmann W.M.
        Efficacy and safety of Eucerin 10% urea lotion in the treatment of symptoms of aged skin.
        J Dermatolog Treat. 1998; 9: 175-179
        • Frithz A.
        Investigation of Cortesal, a hydrocortisone cream and its water-retaining cream base in the treatment of xerotic skin and dry eczemas.
        Curr Ther Res. 1983; 33: 930-935
        • Grice K.
        • Sattar H.
        • Baker H.
        Urea and retinoic acid in ichthyosis and their effect on transepidermal water loss and water holding capacity of stratum corneum.
        Acta Derm Venereol (Stockh). 1973; 54: 114-118
        • Kuster W.
        • Bohnsack K.
        • Rippke F.
        • Upmeyer H.J.
        • Groll S.
        • Traupe H.
        Efficacy of urea therapy in children with ichthyosis. A multicenter randomized, placebo-controlled, double-blind, semilateral study.
        Dermatology. 1998; 196: 217-222
        • Serup J.A.
        double-blind comparison of two creams containing urea as the active ingredient. Assessment of efficacy and side-effects by non-invasive techniques and a clinical scoring scheme.
        Acta Derm Venereol Suppl. 1992; 177: 34-43
        • Batt M.D.
        • Davis W.B.
        • Fairhurst E.
        • Gerreard W.A.
        • Ridge B.D.
        Changes in the physical properties of the stratum corneum following treatment with glycerol.
        J Soc Cosmet Chem. 1988; 39: 367-381
        • Swanbeck G.
        A new treatment of ichthyosis and other hyperkeratotic conditions.
        Acta Derm Venereol (Stockh). 1968; 48: 123-127
        • Tagami H.
        Electrical measurement of the water content of the skin surface. Functional analysis of the hygroskopic property and water-holding capacity of the stratum corneum in vivo and technique for assessing moisturizing efficacy.
        Cosmet Toiletries. 1982; 97: 39-47
        • Pope F.M.
        • Rees J.K.
        • Wells R.S.
        • Lewis K.G.S.
        Out-patient treatment of ichthyosis: a double-blind trial of of ointments.
        Br J Dermatol. 1972; 86: 291-296
        • Alderson S.G.
        • Barratt M.G.
        • Black J.G.
        Effect of 2-hydroxyacids on guinea-pig footpad stratum corneum: mechanical properties and binding studies.
        Int J Cosmet Sci. 1984; 6: 91
        • Takahashi M.
        • Machida Y.
        • Tsuda Y.
        The influence of hydroxy acids on the rheological properties of stratum corneum.
        J Soc Cosmet Chem. 1985; 36: 177-187
        • Hall K.J.
        • Hill J.C.
        The skin plasticisation effect of 2-hydroxyoctanoic acid. 1: the use of potentiators.
        J Soc Cosmet Chem. 1986; 37: 397-407
        • Jokura Y.
        • Ishikawa S.
        • Tokuda H.
        • Imokawa G.
        Molecular analysis of elastic properties of the stratum corneum by solid-state 13C-nuclear magnetic resonance spectroscopy.
        J Invest Dermatol. 1995; 104: 806-812
        • Horii I.
        • Nakayama Y.
        • Obata M.
        • Tagami H.
        Stratum corneum hydration and amino acid content in xerotic skin.
        Br J Dermatol. 1989; 121: 587-592
        • Denda M.
        • Hori J.
        • Koyama J.
        • et al.
        Stratum corneum sphingolipids and free amino acids in experimentally-induced scaly skin.
        Arch Dermatol Res. 1992; 284: 363-367
        • Van Scott E.J.
        • Yu R.J.
        Hyperkeratinization, corneocyte cohesion, and alpha hydroxy acids.
        J Am Acad Dermatol. 1984; 11: 867-879
        • Smith W.P.
        Comparative effectiveness of alfa-hydroxy acids on skin properties.
        Int J Cosmet Sci. 1996; 18: 75-83
        • Thueson D.O.
        • Chan E.K.
        • Oechsli L.M.
        • Hahn G.S.
        The roles of pH and concentration in lactic acid-induced stimulation of epidermal turnover.
        Dermatol Surg. 1998; 24: 641-645
        • Yu R.J.
        • Van Scott E.J.
        Alpha-hydroxy acids: science and therapeutic use.
        Cosmet Dermatol. 1994; : 1-6
        • Van Scott E.J.
        • Yu R.J.
        Control of keratinization with alpha-hydroxy acids and related compounds. I. Topical treatment of ichthyotic disorders.
        Arch Dermatol. 1974; 110: 586-590
        • Blair C.
        The action of a urea-lactic acid ointment in ichthyosis. With particular reference to the thickness of the horny layer.
        Br J Dermatol. 1976; 94: 145-153
        • Norlén L.
        • Emilson A.
        • Forslind B.
        Stratum corneum swelling. Biophysical and computer assisted quantitative assessments.
        Arch Dermatol Res. 1997; 289: 506-513
        • Caussin J.
        • Groenink H.W.
        • de Graaff A.M.
        • et al.
        Lipophilic and hydrophilic moisturizers show different actions on human skin as revealed by cryo scanning electron microscopy.
        Exp Dermatol. 2007; 16: 891-898
        • Fluhr J.
        • Bornkessel A.
        • Berardesca E.
        Glycerol—just a moisturizer? Biological and biophysical effects.
        in: Lodén M. Maibach H.I. Dry skin and moisturizers. Chemistry and function. 2nd ed. Taylor & Francis Group, Boca Raton2005: 227-243
        • Rawlings A.V.
        • Harding C.
        • Watkinson A.
        • Banks J.
        • Ackerman C.
        • Sabin R.
        The effect of glycerol and humidity on desmosome degradation in stratum corneum.
        Arch Dermatol Res. 1995; 287: 457-464
        • Froebe C.L.
        • Simion F.A.
        • Ohlmeyer H.
        • et al.
        Prevention of stratum corneum lipid phase transitions in vitro by glycerol -An alternative mechanism for skin moisturization.
        J Soc Cosmet Chem. 1990; 41: 51-65
        • Mattai J.
        • Froebe C.L.
        • Rhein L.D.
        • et al.
        Prevention of model stratum corneum lipid phase transitions in vitro by cosmetic additives—differential scanning calometry, optical microscopy, and water evaporation studies.
        J Soc Cosmet Chem. 1993; 44: 89-100
        • Costa-Balogh F.O.
        • Wennerstrom H.
        • Wadso L.
        • Sparr E.
        How small polar molecules protect membrane systems against osmotic stress: the urea-water-phospholipid system.
        J Phys Chem B. 2006; 110: 23845-23852
        • Batt M.D.
        • Fairhurst E.
        Hydration of the stratum corneum.
        Int J Cosmet Sci. 1986; 8: 253-264
        • Wellner K.
        • Wohlrab W.
        Quantitative evaluation of urea in stratum corneum of human skin.
        Arch Dermatol Res. 1993; 285: 239-240
        • Brandner J.M.
        Pores in the epidermis: aquaporins and tight junctions.
        Int J Cosmet Sci. 2007; 29: 413-422
        • Lundstrom A.
        • Egelrud T.
        Cell shedding from human plantar skin in vitro: evidence of its dependence on endogenous proteolysis.
        J Invest Dermatol. 1988; 91: 340-343
        • Blank I.H.
        • Moloney J.
        • Emslie A.G.
        • Simon I.
        • Apt C.
        The diffusion of water across the stratum corneum as a function of its water content.
        J Invest Dermatol. 1984; 82: 188-194
        • Lodén M.
        Prevention or promotion of dryness and eczema by moisturizers?.
        Expert Rev Dermatol. 2008; 3: 667-676
        • Lodén M.
        Urea-containing moisturizers influence barrier properties of normal skin.
        Arch Dermatol Res. 1996; 288: 103-107
        • Hachem J.P.
        • De Paepe K.
        • Vanpée E.
        • Kaufman L.
        • Rogiers V.
        • Roseeuw D.
        The effect of two of moisturisers on skin barrier damage in allergic contact dermatitis.
        Eur J Dermatol. 2002; 12: 136-138
        • Duval D.
        • Lindberg M.
        • Boman A.
        • Johansson S.
        • Edlund F.
        • Lodén M.
        Differences among moisturizers in affecting skin susceptibility to hexyl nicotinate, measured as time to increase skin blood flow.
        Skin Res Technol. 2002; 8: 1-5
        • Buraczewska I.
        • Lodén M.
        Treatment of surfactant-damaged skin in humans with creams of different pH.
        Pharmacology. 2005; 73: 1-7
        • Levin J.
        • Maibach H.
        Human skin buffering capacity: an overview.
        Skin Res Technol. 2008; 14: 121-126
        • Lodén M.
        Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream.
        Contact Dermatitis. 1997; 36: 256-260
        • Lodén M.
        • Bárány E.
        • Mandahl P.
        • Wessman C.
        The influence of urea treatment on skin susceptibility to surfactant-induced irritation: a placebo-controlled and randomized study.
        Exog Dermatol. 2004; 3: 1-6
        • Lodén M.
        • Wessman C.
        The influence of a cream containing 20% glycerin and its vehicle on skin barrier properties.
        Int J Cosmet Sci. 2001; 23: 115-120
        • Lindberg M.
        • Forslind B.
        The skin as a barrier.
        in: Loden M. Maibach H.I. Dry skin and moisturizers. Chemistry and function. CRC Press Taylor & Francis Group, Boca Raton2005: 9-21
        • Bouwstra J.A.
        • Gooris G.S.
        • Dubbelaar F.E.
        • Weerheim A.M.
        • Ponec M.
        pH, cholesterol sulfate, and fatty acids affect the stratum corneum lipid organization.
        J Investig Dermatol Symp Proc. 1998; 3: 69-74
        • Pilgram G.S.
        • van der Meulen J.
        • Gooris G.S.
        • Koerten H.K.
        • Bouwstra J.A.
        The influence of two azones and sebaceous lipids on the lateral organization of lipids isolated from human stratum corneum.
        Biochim Biophys Acta. 2001; 1511: 244-254
        • Tsang M.
        • Guy R.H.
        Effect of Aqueous Cream BP on human stratum corneum in vivo.
        Br J Dermatol. 2010; 163: 954-958
        • Buraczewska I.
        • Berne B.
        • Lindberg M.
        • Loden M.
        • Torma H.
        Long-term treatment with moisturizers affects the mRNA levels of genes involved in keratinocyte differentiation and desquamation.
        Arch Dermatol Res. 2009; 301: 175-181
        • Weinberg W.C.
        • Denning M.F.
        P21Waf1 control of epithelial cell cycle and cell fate.
        Crit Rev Oral Biol Med. 2002; 13: 453-464
        • Chang B.D.
        • Watanabe K.
        • Broude E.V.
        • et al.
        Effects of p21Waf1/Cip1/Sdi1 on cellular gene expression: implications for carcinogenesis, senescence, and age-related diseases.
        Proc Natl Acad Sci U S A. 2000; 97: 4291-4296
        • Buraczewska I.
        • Berne B.
        • Lindberg M.
        • Loden M.
        • Torma H.
        Moisturizers change the mRNA expression of enzymes synthesizing skin barrier lipids.
        Arch Dermatol Res. 2009; 301: 587-594
        • Ekholm I.E.
        • Brattsand M.
        • Egelrud T.
        Stratum corneum tryptic enzyme in normal epidermis: a missing link in the desquamation process?.
        J Invest Dermatol. 2000; 114: 56-63
        • Ekholm E.
        • Egelrud T.
        Expression of stratum corneum chymotryptic enzyme in relation to other markers of epidermal differentiation in a skin explant model.
        Exp Dermatol. 2000; 9: 65-70
        • Fluhr J.W.
        • Gloor M.
        • Lehmann L.
        • Lazzerini S.
        • Distante F.
        • Berardesca E.
        Glycerol accelerates recovery of barrier function in vivo.
        Acta Derm Venereol. 1999; 79: 418-421
        • Held E.
        • Lund H.
        • Agner T.
        Effect of different moisturizers on SLS-irritated human skin.
        Contact Dermatitis. 2001; 44: 229-234
        • Kucharekova M.
        • Schalkwijk J.
        • Van de Kerkhof P.C.M.
        • Van de Valk P.G.
        Effect of a lipid-rich emollient containing ceramide 3 in experimentally induced skin barrier dysfunction.
        Contact Dermatitis. 2002; 46: 331-338
        • Mortz C.G.
        • Andersen K.E.
        • Halkier-Sørensen L.
        The efficacy of different moisturizers on barrier recovery in hairless mice evaluated by non-invasive bioengineering methods. A model to select the potentially most effective product.
        Contact Dermatitis. 1997; 36: 297-310
        • Zettersten E.M.
        • Ghadially R.
        • Feingold K.R.
        • Crumrine D.
        • Elias P.M.
        Optimal ratios of topical stratum corneum lipids improve barrier recovery in chronologically aged skin.
        J Am Acad Dermatol. 1997; 37: 403-408
        • Ghadially R.
        • Halkier_Sorensen L.
        • Elias P.M.
        Effects of petrolatum on stratum corneum structure and function.
        J Am Acad Dermatol. 1992; 26: 387-396
        • Lodén M.
        • Barany E.
        Skin-identical lipids versus petrolatum in the treatment of tape-stripped and detergent-perturbed human skin.
        Acta Derm Venereol. 2000; 80: 412-415
        • Chamlin S.L.
        • Kao J.
        • Frieden I.J.
        • et al.
        Ceramide-dominant barrier repair lipids alleviate childhood atopic dermatitis: changes in barrier function provide a sensitive indicator of disease activity.
        J Am Acad Dermatol. 2002; 47: 198-208
        • Man M.M.
        • Feingold K.R.
        • Thornfeldt C.R.
        • Elias P.M.
        Optimization of physiological lipid mixtures for barrier repair.
        J Invest Dermatol. 1996; 106: 1096-1101
        • De Paepe K.
        • Derde M.P.
        • Reseeuw D.
        • Rogiers V.
        Incorporation of ceramide 3B in dermatocosmetic emulsions: effect of the transepidermal water loss of sodium lauryl sulphate-damaged skin.
        JAEDV. 2000; 14: 272-279
        • Barany E.
        • Lindberg M.
        • Lodén M.
        Unexpected skin barrier influence from nonionic emulsifiers.
        Int J Pharm. 2000; 195: 189-195
        • Proksch E.
        • Nissen H.P.
        Dexpanthenol enhances skin barrier repair and reduces inflammation after sodium lauryl sulphate-induced irritation.
        J Dermatol Treat. 2002; 13: 173-178
        • Tanno O.
        • Ota Y.
        • Kitamura N.
        • Katsube T.
        • Inoue S.
        Nicotinamide increases biosynthesis of ceramides as well as other stratum corneum lipids to improve the epidermal permeability barrier.
        Br J Dermatol. 2000; 143: 524-531
        • Summers R.S.
        • Summers B.
        • Chandar P.
        • Feinberg C.
        • Gursky R.
        • Rawlings A.V.
        The effect of lipids, with and without humectant, on skin xerosis.
        J Soc Cosmet Chem. 1996; 47: 27-39
        • Draelos Z.D.
        Moisturizing cream ameliorates dryness and desquamation in participants not receiving topical psoriasis treatment.
        Cutis. 2008; 82: 211-216
        • Halkier-Sorensen L.
        • Thestrup-Pedersen K.
        The efficacy of a moisturizer (Locobase) among cleaners and kitchen assistants during everyday exposure to water and detergents.
        Contact Dermatitis. 1993; 29: 266-271
        • Lodén M.
        • Andersson A.C.
        • Andersson C.
        • Frodin T.
        • Oman H.
        • Lindberg M.
        Instrumental and dermatologist evaluation of the effect of glycerine and urea on dry skin in atopic dermatitis.
        Skin Res Technol. 2001; 7: 209-213
        • Kikuchi K.
        • Tagami H.
        Noninvasive biophysical assessments of the efficacy of a moisturizing cosmetic cream base for patients with atopic dermatitis during different seasons.
        Br J Dermatol. 2008; 158: 969-978
        • Andersson A.-C.
        • Lindberg M.
        • Lodén M.
        The effect of two urea-containing creams on dry, eczematous skin in atopic patients. I. Expert, patient and instrumental evaluation.
        J Dermatol Treat. 1999; 10: 165-169
        • Lodén M.
        • Andersson A.-C.
        • Lindberg M.
        Improvement in skin barrier function in patients with atopic dermatitis after treatment with a moisturizing cream (Canoderm).
        Br J Dermatol. 1999; 140: 264-267
        • Sasaki Y.
        • Tadaki T.
        • Tagami H.
        The effects of a topical application of urea cream on the function of pathological stratum corneum.
        Acta Dermatol Kyoto. 1989; 84: 581
        • Berardesca E.
        • Vignoli G.P.
        • Distante F.
        • Rona C.
        Effects of glycolic acid on psoriasis.
        Clin Exp Dermatol. 1998; 23: 189
        • Rawlings A.V.
        • Davies A.
        • Carlomusto M.
        • et al.
        Effect of lactic acid isomers on keratinocyte ceramide synthesis, stratum corneum lipid levels and stratum corneum barrier function.
        Arch Dermatol Res. 1996; 288: 383-390
        • Berardesca E.
        • Distante F.
        • Vignoli G.P.
        • Oresajo C.
        • Green B.
        Alpha hydroxyacids modulate stratum corneum barrier function.
        Br J Dermatol. 1997; 137: 934-938
        • Gånemo A.
        • Virtanen M.
        • Vahlquist A.
        Improved topical treatment of lamellar ichthyosis: a double blind study of four different cream formulations.
        Br J Dermatol. 1999; 141: 1027-1032
        • Kolbe L.
        • Kligman A.M.
        • Stoudemayer T.
        Objective bioengineering methods to assess the effects of moisturizers on xerotic leg of elderly people.
        J Dermatol Treat. 2000; 11: 241-245
        • Lucky A.W.
        • Leach A.D.
        • Laskarzewski P.
        • Wenck H.
        Use of an emollient as a steroid-sparing agent in the treatment of mild to moderate atopic dermatitis in children.
        Pediatr Dermatol. 1997; 14: 321-324
        • Giordano-Labadie F.
        • Cambazard F.
        • Guillet G.
        • Combemale P.
        • Mengeaud V.
        Evaluation of a new moisturizer (Exomega milk) in children with atopic dermatitis.
        J Dermatol Treat. 2006; 17: 78-81
        • Draelos Z.D.
        The effect of ceramide-containing skin care products on eczema resolution duration.
        Cutis. 2008; 81: 87-91
        • 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
        • Szczepanowska J
        • Reich A
        • Szepietowski JC
        Emollients improve treatment results with topical corticosteroids in childhood atopic dermatitis: a randomized comparative study.
        Pediatr Allergy Immunol. 2008; 19: 614-618
        • Wirén K.
        • Nohlgård C.
        • Nyberg F.
        • et al.
        Treatment with a barrier-strengthening moisturizing cream delays relapse of atopic dermatitis: a prospective and randomized controlled clinical trial.
        J Eur Acad Dermatol Venereol. 2009; 23: 1267-1272
        • Loden M.
        • Wiren K.
        • Smerud K.
        • et al.
        Treatment with a barrier-strengthening moisturizer prevents relapse of hand-eczema. An open, randomized, prospective, parallel group study.
        Acta Derm Venereol. 2010; 90: 602-606
        • Gollnick H.
        • Kaufmann R.
        • Stough D.
        • et al.
        Pimecrolimus cream 1% in the long-term management of adult atopic dermatitis: prevention of flare progression. A randomized controlled trial.
        Br J Dermatol. 2008; 158: 1083-1093
        • Meurer M.
        • Folster-Holst R.
        • Wozel G.
        • Weidinger G.
        • Junger M.
        • Brautigam M.
        Pimecrolimus cream in the long-term management of atopic dermatitis in adults: a six-month study.
        Dermatology. 2002; 205: 271-277
        • Wollenberg A.
        • Reitamo S.
        • Girolomoni G.
        • et al.
        Proactive treatment of atopic dermatitis in adults with 0.1% tacrolimus ointment.
        Allergy. 2008; 63: 742-750
        • Meurer M.
        • Fartasch M.
        • Albrecht G.
        • et al.
        Long-term efficacy and safety of pimecrolimus cream 1% in adults with moderate atopic dermatitis.
        Dermatology. 2004; 208: 365-372
        • Berth-Jones J.
        • Damstra R.J.
        • Golsch S.
        • et al.
        Twice weekly fluticasone propionate added to emollient maintenance treatment to reduce risk of relapse in atopic dermatitis: randomised, double blind, parallel group study.
        BMJ. 2003; 326: 1367
        • van den Oord R.A.
        • Sheikh A.
        Filaggrin gene defects and risk of developing allergic sensitisation and allergic disorders: systematic review and meta-analysis.
        BMJ. 2009; 339: b2433