American Journal of Clinical Dermatology

, Volume 5, Issue 4, pp 217–223 | Cite as

Stratum Corneum pH in Atopic Dermatitis

Impact on Skin Barrier Function and Colonization with Staphylococcus Aureus
  • Frank Rippke
  • Volker Schreiner
  • Thomas Doering
  • Howard I. Maibach
Leading Article


Recent studies have provided new insights into the occurrence, causes, and pathogenetic consequences of changes in the skin pH in atopic dermatitis, particularly with respect to skin barrier function and colonization with Staphylococcus aureus. Growing evidence suggests an impaired release of proton donors, such as amino acids, urocanic acid, and lactic acid, to the stratum corneum in atopic dermatitis, as a result of reductions in filaggrin proteolysis and sweat secretion. In addition, an impaired formation of free fatty acids from sebaceous lipids and epidermal phospholipids seems to be involved. Because both lipid organization and lipid metabolism in the stratum corneum requires an acidic pH, these alterations might contribute to the disturbance of skin barrier function observed in atopic dermatitis. Furthermore, bacterial growth and virulence of S. aureus, as well as defensive host mechanisms, have increasingly been delineated as pH dependent, giving rise to a new understanding of the pathophysiology underlying increased skin colonization seen in atopic dermatitis.


Atopic Dermatitis Stratum Corneum Lamellar Body Skin Barrier Function Stratum Corneum Lipid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors have provided no information on sources of funding or on conflicts of interest directly relevant to the content of this review.


  1. 1.
    Rippke F, Schreiner V, Schwanitz HJ. The acidic milieu of the horny layer: new findings on the physiology and pathophysiology of the skin pH. Am J Clin Dermatol 2002; 3: 261–72PubMedCrossRefGoogle Scholar
  2. 2.
    Elias PM, Williams ML, Feingold KR. Beyond the lymphocyte: in defense of skin defence. In: Paus R, editor. What is the “true” function of skin? Exp Dermatol 2002; 11: 165–8CrossRefGoogle Scholar
  3. 3.
    Mauro T, Holleran WM, Grayson S, et al. Barrier recovery is impeded at neutral pH, independent of ionic effects: implications for extracellular lipid processing. Arch Dermatol Res 1998; 290: 215–22PubMedCrossRefGoogle Scholar
  4. 4.
    Yosipovitch G, Maibach HI. Skin surface pH: a protective acid mantle. Cosmet Toiletr 1996; 111: 101–2Google Scholar
  5. 5.
    Parra JL, Paye M, The EEMCO Group. EEMCO guidance for the in vivo assessment of skin surface pH. Skin Pharmacol Appl Skin Physiol 2003; 16: 188–202PubMedGoogle Scholar
  6. 6.
    Braun-Falco O, Korting HC. Der normale pH-Wert der menschlichen Haut. Hautarzt 1986; 37: 126–9PubMedGoogle Scholar
  7. 7.
    Fluhr JW, Elias PM. Stratum corneum pH: formation and function of the “acid mantle”. Exog Dermatol 2002; 1: 163–75CrossRefGoogle Scholar
  8. 8.
    Chapman SJ, Walsh A. Membrane-coating granules are acidic organelles which possess proton pumps. J Invest Dermatol 1989; 93: 466–70PubMedCrossRefGoogle Scholar
  9. 9.
    Behne MJ, Meyer J, Hanson KM, et al. NHE1 regulates the stratum corneum permeability barrier homeostasis: microenvironment acidification assessed with fluorescence lifetime imaging. J Biol Chem 2002; 277: 47399–406PubMedCrossRefGoogle Scholar
  10. 10.
    Tagami H, Kobayashi H, Zhen X-S, et al. Environmental effects on the functions of the stratum corneum. J Invest Dermatol Symp Proc 2001; 6: 87–94CrossRefGoogle Scholar
  11. 11.
    Diepgen TL, Fartasch M, Hornstein O. Evaluation and relevance of atopic basic and minor features in patients with atopic dermatitis and the general population. Acta Derm Venereol Suppl (Stockh) 1989; 144: 50–4Google Scholar
  12. 12.
    Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Dermatol Venereol (Stockh) 1980; 92: 44–7Google Scholar
  13. 13.
    Eberlein-König B, Schäfer T, Huss-Marp J, et al. Skin surface pH, stratum corneum hydration, trans-epidermal water loss and skin roughness related to atopic eczema and skin dryness in a population of primary school children. Acta Derm Venereol 2000; 80: 188–91PubMedCrossRefGoogle Scholar
  14. 14.
    Seidenari S, Giusti G. Objective assessment of the skin of children affected by atopic dermatitis: a study of pH, capacitance and TEWL in eczematous and clinically uninvolved skin. Acta Derm Venereol (Stockh) 1995; 75: 429–33Google Scholar
  15. 15.
    Sparavigna A, Setaro M, Gualandri V. Cutaneous pH in children affected by atopic dermatitis and in healthy children: a multicenter study. Skin Res Technol 1999; 5: 221–7CrossRefGoogle Scholar
  16. 16.
    O’Goshi K, Okada M, Iguchi M, et al. The predilection sites for chronic atopic dermatitis do not show any special functional uniqueness of the stratum corneum. Exog Dermatol 2002; 1: 195–202CrossRefGoogle Scholar
  17. 17.
    Rügemer J, Wirtz P, Hellermann M, et al. Messung der hautphysiologischen Parameter Wassergehalt, pH-Wert und TEWL bei Kindern mit atopischem Ekzem und einer hautgesunden Kontrollgruppe [abstract]. Z Hautkr 2001; 76 Suppl. 1: S70–1Google Scholar
  18. 18.
    Stalder JF, Taieb A, Atherton DJ, et al. Severity scoring of atopic dermatitis: the SCORAD index. Dermatology 1993; 186: 23–31CrossRefGoogle Scholar
  19. 19.
    Choi SJ, Song MG, Sung WT, et al. Comparison of transepidermal water loss, capacitance and pH values in the skin between intrinsic and extrinsic atopic dermatitis. J Korean Med Sci 2003; 18: 93–6PubMedGoogle Scholar
  20. 20.
    Conti A, Di Nardo A, Seidenari S. No alteration of biophysical parameters in the skin of subjects with respiratory atopy. Dermatology 1996; 192: 317–20PubMedCrossRefGoogle Scholar
  21. 21.
    Rajka G. Surface lipid estimation on the back of hands in atopic dermatitis. Arch Dermatol Forsch 1974; 251: 43–8PubMedGoogle Scholar
  22. 22.
    Bleck O, Abeck D, Ring J, et al. Two ceramide subfractions detectable in CER(AS) position HPTLC in skin surface lipids of non-lesional skin of atopic eczema. J Invest Dermatol 1999; 113: 894–900PubMedCrossRefGoogle Scholar
  23. 23.
    Melnik B, Hollmann J, Hofmann U, et al. Lipid composition of outer stratum corneum and nails in atopic and control subjects. Arch Dermatol Res 1990; 282: 549–51PubMedCrossRefGoogle Scholar
  24. 24.
    Melnik BC. Disturbances of epidermal lipid metabolism and barrier function in atopic eczema. In: Ruzicka T, Ring J, Przybilla B, editors. Handbook of atopic eczema. Berlin: Springer, 1991: 296–305Google Scholar
  25. 25.
    Parkkinen MU, Kiistala R, Kiistala U. Sweating response to moderate thermal stress in atopic dermatitis. Br J Dermatol 1992; 126: 346–50PubMedCrossRefGoogle Scholar
  26. 26.
    Stern UM, Hornstein OP, Salzer B. Do training-dependent differences in perspiration exist between healthy and atopic subjects? J Dermatol 2000; 27: 491–9PubMedGoogle Scholar
  27. 27.
    Liebke C, Wahn U, Niggemann B. Sweat electrolyte concentrations in children with atopic dermatitis. Lancet 1997; 350: 1678–9PubMedCrossRefGoogle Scholar
  28. 28.
    Schwarz E. Neurodermitis und Hornschicht. Z Hautkr 1977; 52 Suppl. 2: 59–64PubMedGoogle Scholar
  29. 29.
    Tanaka M, Okada M, Zhen YX, et al. Decreased hydration state of the stratum corneum and reduced amino acid content of the skin surface in patients with seasonal allergic rhinitis. Br J Dermatol 1998; 139: 618–21PubMedCrossRefGoogle Scholar
  30. 30.
    Watanabe M, Tagami H, Horii I, et al. Functional analyses of the superficial stratum corneum in atopic xerosis. Arch Dermatol 1991; 127: 1689–92PubMedCrossRefGoogle Scholar
  31. 31.
    Seguchi T, Chang-Yi C, Kusuda S, et al. Decreased expression of filaggrin in atopic skin. Arch Dermatol Res 1996; 288: 442–6PubMedCrossRefGoogle Scholar
  32. 32.
    Abeck D, Stäb F, Keyhani A, et al. Antioxidant- and urocanic acid status in atopic eczema [abstract]. J Invest Dermatol 1994; 103: 417Google Scholar
  33. 33.
    Abeck D, Lauer W, Schmidt T, et al. Age-dependent differences of histidine-, urocanic acid and urocanic isomers concentration in atopic eczema [abstract]. J Invest Dermatol 1996; 107: 468Google Scholar
  34. 34.
    Taieb A, Montaudon D, Loos P, et al. Urocanic acid: a link between atopic dermatitis and ichthyosis vulgaris? In: Czernielewski JM, editor. Immunological and pharmacological aspects of atopic and contact eczema: pharmacology and the skin. Vol. 4. Basel: Karger, 1991: 184–7Google Scholar
  35. 35.
    Fartasch M, Diepgen TL. The barrier function in atopic dry skin: disturbance of membrane-coating granule exocytosis and formation of epidermal lipids? Acta Derm Venereol Suppl (Stockh) 1992; 176: 26–31Google Scholar
  36. 36.
    Patel SD, Noble WC. Analyses of skin surface lipid in patients with microbiologically associated skin disease. Clin Exp Dermatol 1993; 18: 405–9PubMedCrossRefGoogle Scholar
  37. 37.
    Gloor M. Sebaceous gland activity in atopic eczema. In: Ruzicka T, Ring J, Przybilla B, editors. Handbook of atopic eczema. Berlin: Springer, 1991: 287–95Google Scholar
  38. 38.
    Fluhr JW, Kao J, Jain M, et al. Generation of free fatty acids from phospholipids regulates stratum corneum acidification and integrity. J Invest Dermatol 2001; 117: 44–51PubMedCrossRefGoogle Scholar
  39. 39.
    Schäfer L, Kragballe K. Abnormalities in epidermal lipid metabolism in patients with atopic dermatitis. J Invest Dermatol 1991; 96: 10–5PubMedCrossRefGoogle Scholar
  40. 40.
    Tarroux R, Assalit MF, Licu D, et al. Variability of enzyme markers during clinical regression of atopic dermatitis. Skin Pharmacol Appl Skin Physiol 2002; 15: 55–62PubMedGoogle Scholar
  41. 41.
    Hara J, Higuchi K, Okamoto R, et al. High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. J Invest Dermatol 2000; 115: 406–13PubMedCrossRefGoogle Scholar
  42. 42.
    Beck JS, Coulson HF, Dove N, et al. Evidence for sodium-coupled acid-base transport across the basolateral membrane of the reabsorptive duct of the human eccrine sweat gland. J Invest Dermatol 2001; 117: 877–9PubMedCrossRefGoogle Scholar
  43. 43.
    Patterson MJ, Galloway SDR, Nimmo MA. Variations in regional sweat composition in normal human males. Exp Physiol 2000; 85 (6): 869–75PubMedCrossRefGoogle Scholar
  44. 44.
    Krien PM, Kermici M. Evidence for the existence of a self-regulating enzymatic process within the human stratum corneum: an unexpected role for urocanic acid. J Invest Dermatol 2000; 115: 414–20PubMedCrossRefGoogle Scholar
  45. 45.
    Imokawa G, Abe A, Jin K, et al. Decreased levels of ceramides in stratum corneum of atopic dermatitis: an etiological factor in atopic dry skin? J Invest Dermatol 1991; 96: 523–6PubMedCrossRefGoogle Scholar
  46. 46.
    Macheleidt O, Kaiser HW, Sandhoff K. Deficiency of epidermal protein-bound ω-hydroxyceramide in atopic dermatitis. J Invest Dermatol 2002; 119: 166–73PubMedCrossRefGoogle Scholar
  47. 47.
    Yamamoto A, Serizawa S, Ito M. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res 1991; 283: 219–23PubMedCrossRefGoogle Scholar
  48. 48.
    Schmuth M, Man MQ, Weber F, et al. Permeability barrier disorder in Niemann-Pick disease: spingomyelin-ceramide processing required for normal barrier homeostasis. J Invest Dermatol 2000; 115: 459–66PubMedCrossRefGoogle Scholar
  49. 49.
    Jin K, Higaki Y, Takagi Y, et al. Analysis of β-glucocerebrosidase and ceramidase activities in atopic and aged skin. Acta Derm Venereol (Stockh) 1994; 74: 337–40Google Scholar
  50. 50.
    Redoules D, Tarroux R, Assalit MF, et al. Characterisation and assay of five enzymatic activities in the stratum corneum using tape-strippings. Skin Pharmacol Appl Skin Physiol 1999; 12: 182–92PubMedGoogle Scholar
  51. 51.
    Kusuda S, Chang-Yi C, Takahashi M, et al. Localization of sphingomyelinase in lesional skin of atopic dermatitis patients. J Invest Dermatol 1998; 111: 733–8PubMedCrossRefGoogle Scholar
  52. 52.
    Bouwstra JA, Gooris GS, Dubbelaar FER, et al. pH, cholesterol sulfate, and fatty acids affect the stratum corneum lipid organization. J Invest Dermatol Symp Proc 1998; 3: 69–74Google Scholar
  53. 53.
    Friberg SE. Micelles, microemulsions, liquid crystals, and the structure of stratum corneum lipids. J Soc Cosmet Chem 1990; 41: 155–71Google Scholar
  54. 54.
    Lieckfeldt R, Villalain J, Gomez-Fernandez J-C, et al. Apparent pKa of the fatty acids within ordered mixtures of model human stratum corneum lipids. Pharm Res 1995; 12: 1614–7PubMedCrossRefGoogle Scholar
  55. 55.
    Pilgram GSK, Vissers DCJ, van der Meulen H, et al. Aberrant lipid organization in stratum corneum of patients with atopic dermatitis and lamellar ichthyosis. J Invest Dermatol 2001; 117: 710–7PubMedCrossRefGoogle Scholar
  56. 56.
    Ekholm IE, Brattsand M, Egelrud T. Stratum corneum tryptic enzyme in normal epidermis: a missing link in the desquamation process? J Invest Dermatol 2000; 114: 56–63PubMedCrossRefGoogle Scholar
  57. 57.
    Hansson L, Bäckmann A, Ny A, et al. Epidermal over expression of stratum corneum chymotryptic enzyme in mice: a model for chronic itchy dermatitis. J Invest Dermatol 2002; 118: 444–9PubMedCrossRefGoogle Scholar
  58. 58.
    Hachem JA, Fowler AJ, Behne M, et al. Increased stratum corneum pH promotes activation and release of primary cytokines from the stratum corneum attributable to activation of serine proteases [abstract]. J Invest Dermatol 2002; 118: 258Google Scholar
  59. 59.
    Abeck D, Mempel M. Cutaneous Staphylococcus aureus colonisation of atopic eczema: mechanisms, pathophysiological importance and therapeutical consequences [in German]. Hautarzt 1998; 49: 902–6PubMedCrossRefGoogle Scholar
  60. 60.
    Korting HC, Bau A, Baldauf P. pH-Abhängigkeit des Wachstumsverhaltens von Staphylococcus aureus und Propionibacterium acnes. Ärztl Kosmetol 1987; 17: 41–53Google Scholar
  61. 61.
    Whiting RC, Sackitey S, Calderone S, et al. Model for the survival of Staphylococcus aureus in non growth environments. Int J Food Microbiol 1996; 31: 231–43PubMedCrossRefGoogle Scholar
  62. 62.
    Gianuzzi L, Contreras E, Zaritzky N. Modeling the aerobic growth and decline of Staphylococcus aureus as affected by pH and potassium sorbate concentration. J Food Prot 1999; 62: 356–62Google Scholar
  63. 63.
    Akiyama H, Yamasaki O, Tada J, et al. Antimicrobial effects of acidic hot-spring water on Staphylococcus aureus strains isolated from atopic dermatitis patients. J Dermatol Sci 2000; 24: 112–8PubMedCrossRefGoogle Scholar
  64. 64.
    Miller SJ, Aly R, Shinefeld HR, et al. In vitro and in vivo antistaphylococcal activity of human stratum corneum lipids. Arch Dermatol 1988; 124: 209–15PubMedCrossRefGoogle Scholar
  65. 65.
    Ushijima T, Takahashi M, Ozaki Y. Acetic, propionic, and oleic acid as the possible factors influencing the predominant residence of some species of Propionibacterium and coagulase-negative Staphylococcus on normal human skin. Can J Microbiol 1984; 30: 647–52PubMedCrossRefGoogle Scholar
  66. 66.
    Kumaran D, Eswaramoorthy S, Furey W, et al. Structure of staphylococcal enterotoxin C2 at various pH levels. Acta Crystallogr D Biol Crystallogr 2001; 57: 1270–5PubMedCrossRefGoogle Scholar
  67. 67.
    Mempel M, Schmidt T, Weidinger S, et al. Role of Staphylococcus aureus surface-associated proteins in the attachment to cultured HaCaT keratinocytes in a new adhesion assay. J Invest Dermatol 1998; 111: 452–6PubMedCrossRefGoogle Scholar
  68. 68.
    Cole GW, Silverberg NL. The adherence of Staphylococcus aureus to human corneocytes. Arch Dermatol 1986; 122: 166–9PubMedCrossRefGoogle Scholar
  69. 69.
    Aly R, Shirley C, Cunico B, et al. Effect of prolonged occlusion on the microbial flora, pH, carbon dioxide and transepidermal water loss on human skin. J Invest Dermatol 1978; 71: 378–81PubMedCrossRefGoogle Scholar
  70. 70.
    Weller R, Price RJ, Ormerod AD. Antimicrobial effect of acidified nitrite on dermatophyte fungi, Candida and bacterial skin pathogens. J Appl Microbiol 2001; 90: 648–52PubMedCrossRefGoogle Scholar
  71. 71.
    Chikakane K, Takahashi H. Measurement of skin pH and its significance in cutaneous diseases. Clin Dermatol 1995; 13: 299–306PubMedCrossRefGoogle Scholar
  72. 72.
    Murakami M, Ohtake T, Dorschner RA, et al. Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. J Invest Dermatol 2002; 119: 1090–5PubMedCrossRefGoogle Scholar
  73. 73.
    Oren A, Ganz T, Liu L, et al. In human epidermis β-defensin 2 is packaged in lamellar bodies. Exp Mol Pathol 2003; 74: 180–4PubMedCrossRefGoogle Scholar
  74. 74.
    Ong PY, Ohtake T, Brandt C, et al. Endogenous antimicrobial peptides and skin infections in atopic dermatitis. N Engl J Med 2002; 347: 1151–60PubMedCrossRefGoogle Scholar
  75. 75.
    Schittek B, Hipfel R, Sauer B, et al. Dermicidin: a novel human antibiotic peptide secreted by sweat glands. Nat Immunol 2001; 2: 1133–7PubMedCrossRefGoogle Scholar
  76. 76.
    Cho S-H, Strickland I, Boguniewicz M, et al. Fibronectin and fibrinogen contribute to the enhanced binding of Staphylococcus aureus to atopic skin. J Allergy Clin Immunol 2001; 108: 269–74PubMedCrossRefGoogle Scholar
  77. 77.
    Bibel DJ, Aly R, Shinefield HR. Topical sphingolipids in antisepsis and antifungal therapy. Clin Exp Dermatol 1995; 20: 395–400PubMedCrossRefGoogle Scholar
  78. 78.
    Arikawa J, Ishibashi M, Kawashima M, et al. Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization with Staphylococcus aureus. J Invest Dermatol 2002; 119: 433–9PubMedCrossRefGoogle Scholar
  79. 79.
    Schmid MH, Korting HC. The concept of the acid mantle of the skin: its relevance for the choice of skin cleansers. Dermatology 1995; 191: 276–80PubMedCrossRefGoogle Scholar
  80. 80.
    Sasai-Takedatsu M, Kojima T, Yamamoto A, et al. Reduction of Staphylococcus aureus in atopic skin lesions with acid electrolytic water: a new therapeutic strategy for atopic dermatitis. Allergy 1997; 52: 1012–6PubMedCrossRefGoogle Scholar
  81. 81.
    Kubota K, Machida I, Tamura K, et al. Treatment of refractory cases of atopic dermatitis with acidic hot-spring bathing. Acta Derm Venereol (Stockh) 1997; 77: 452–4Google Scholar
  82. 82.
    Pigatto PD, Bigardi AS, Cannistraci C, et al. 10% urea cream (Laceran) for atopic dermatitis: a clinical and laboratory evaluation. J Dermatolog Treat 1996; 7: 171–5CrossRefGoogle Scholar
  83. 83.
    Bielfeldt S, Wehmeyer A, Rippke F, et al. Efficacy of a new hand care system (cleansing oil and cream) in a model of irritation and in atopic hand eczema [in German]. Occup Environ 1998; 46: 159–65Google Scholar
  84. 84.
    Tabata N, O’Goshi K, Zhen YX, et al. Biophysical assessment of persistent effects of moisturizers after their daily applications: evaluation of corneotherapy. Dermatology 2000; 200: 308–13PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2004

Authors and Affiliations

  • Frank Rippke
    • 1
  • Volker Schreiner
    • 1
  • Thomas Doering
    • 1
  • Howard I. Maibach
    • 2
  1. 1.Beiersdorf AGHamburgGermany
  2. 2.Department of DermatologyUniversity of California San Francisco Medical CenterSan FranciscoUSA

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