Skip to main content

Advertisement

Log in

Ceramide profiles of the uninvolved skin in atopic dermatitis and psoriasis are comparable to those of healthy skin

  • Original Paper
  • Published:
Archives of Dermatological Research Aims and scope Submit manuscript

Abstract

Ceramides are sphingolipids consisting of sphingoidbases, which are amide-linked to fatty acids. In the stratum corneum, they represent the major constituent of the free extractable intercellular lipids and play a significant role in maintaining and structuring the water permeability barrier of the skin. Using thin layer chromatography, which represents the method of the first choice in analyzing the stratum corneum ceramides, at least seven classes can be distinguished. Each ceramide class contains various species, which have the same head group and different chain lengths. As in many other skin disorders, atopic dermatitis and psoriasis show derangements in content and profile of the ceramides. Such derangements were reported for both the lesional involved as well as for the normal-appearing uninvolved skin. In this study, we focused on investigating the stratum corneum ceramides of the uninvolved skin in atopic dermatitis and psoriasis patients compared to healthy skin. The aim of the investigations was to explore possible significant and specific differences which can be accomplished for purposes of early diagnostics. The skin lipids were collected by means of an in vivo topical extraction procedure using an extraction mixture consisting of n-hexane and ethanol, (2:1). An automated multiple development-high performance thin layer chromatography (AMD-HPTLC) method with photodensitometric detection were applied to separate the ceramides and to estimate their contents. For studying their molecular profile within each ceramide class, a new method of normal phase HPLC with atmospheric pressure chemical ionization mass spectrometry were used. The results obtained by AMD-HPTLC exposed no significant alterations regarding the relative composition of the major stratum corneum lipids and primarily the ceramides. In addition, the mass spectrometric profiles within each ceramide class were similar in the patients and the healthy control subjects. In conclusion, this study revealed that the normal-appearing uninvolved skin of atopic dermatitis and psoriasis patients does not prove significant or specific deficiencies with respect to the free extractable major stratum corneum lipids and mainly the ceramides, when compared to healthy skin. Thus, they cannot be used for diagnostic purposes. Furthermore, our data are not consistent with the concept that impairments in the ceramide composition represent an obligate etiologic factor for both diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Alessandrini F, Stachowitz S, Ring J, Behrendt H (2001) The level of prosaposin is decreased in the skin of patients with psoriasis vulgaris. J Invest Dermatol 116:394–400

    Google Scholar 

  2. Berardesca E, Fideli D, Borroni G, Rabbiosi G, Maibach H (1990) In vivo hydration and water-retention capacity of stratum corneum in clinically uninvolved skin in atopic and psoriatic patients. Acta Derm Venereol 70:400–404

    Google Scholar 

  3. Bleck O, Abeck D, Ring J, Hoppe U, Vietzke JP, Wolber R, Brandt O, Schreiner V (1999) Two ceramide subfractions detectable in Cer(AS) position by HPTLC in skin surface lipids of non-lesional skin of atopic eczema. J Invest Dermatol 113:894–900

    Google Scholar 

  4. Bonte F, Pinguet P, Chevalier JM, Meybeck A (1995) Analysis of all stratum corneum lipids by automated multiple development high-performance thin-layer chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 664:311–316

    Google Scholar 

  5. Bouwstra JA, Gooris GS, Dubbelaar FE, Weerheim AM, Ijzerman AP, Ponec M (1998) Role of ceramide 1 in the molecular organization of the stratum corneum lipids. J Lipid Res 39:186–196

    Google Scholar 

  6. Charman C, Williams H (2000) Outcome measures of disease severity in atopic dermatitis. Arch Dermatol 136:763–769

    Google Scholar 

  7. Coderch L, Lopez O, de la Maza A, Parra JL (2003) Ceramides and skin function. Am J Clin Dermatol 4:107–129

    Google Scholar 

  8. De Paepe K, Weerheim A, Houben E, Roseeuw D, Ponec M, Rogiers V (2004) Analysis of epidermal lipids of the healthy human skin: factors affecting the design of a control population. Skin Pharmacol Physiol 17:23–30

    Google Scholar 

  9. Di Nardo A, Wertz P, Giannetti A, Seidenari S (1998) Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol 78:27–30

    Google Scholar 

  10. Downing DT, Stewart ME, Wertz PW, Colton SW, Abraham W, Strauss JS (1987) Skin lipids: an update. J Invest Dermatol 88:2s–6s

    Google Scholar 

  11. Elias PM (1981) Epidermal lipids, membranes, and keratinization. Int J Dermatol 20:1–19

    Google Scholar 

  12. Farwanah H, Neubert R, Zellmer S, Raith K (2002) Improved procedure for the separation of major stratum corneum lipids by means of automated multiple development thin-layer chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 780:443–450

    Google Scholar 

  13. Farwanah H, Nuhn P, Neubert R, Raith K (2003) Normal-phase liquid chromatographic separation of stratum corneum ceramides with detection by evaporative light scattering and atmospheric pressure chemical ionization mass spectrometry. Anal Chim Acta 492:233–239

    Google Scholar 

  14. Fredriksson T, Petterson U (1978) Severe psoriasis - oral therapy with a new retinoid. Dermatologica 157:238–244

    CAS  PubMed  Google Scholar 

  15. Ghadially R, Brown BE, Sequeira-Martin SM, Feingold KR, Elias PM (1995) The aged epidermal permeability barrier. Structural, functional, and lipid biochemical abnormalities in humans and a senescent murine model. J Clin Invest 95:2281–2290

    Google Scholar 

  16. Grubauer G, Feingold KR, Harris RM, Elias PM (1989) Lipid content and lipid type as determinants of the epidermal permeability barrier. J Lipid Res 30:89–96

    Google Scholar 

  17. Hamanaka S, Hara M, Nishio H, Otsuka F, Suzuki A, Uchida Y (2002) Human epidermal glucosylceramides are major precursors of stratum corneum ceramides. J Invest Dermatol 119:416–423

    Google Scholar 

  18. Hanifin JM, Thurston M, Omoto M, Cherill R, Tofte SJ, Graeber M, Group TEE (2001) The eczema area and severity index (EASI): assessment of reliability in atopic dermatitis. Exp Dermatol 10:11–18

    Google Scholar 

  19. Hara J, Higuchi K, Okamoto R, Kawashima M, Imokawa G (2000) High-expression of sphingomyelin deacylase is an important determinant of ceramide deficiency leading to barrier disruption in atopic dermatitis. J Invest Dermatol 115:406–413

    Google Scholar 

  20. Holleran WM, Man MQ, Gao WN, Menon GK, Elias PM, Feingold KR (1991) Sphingolipids are required for mammalian epidermal barrier function. Inhibition of sphingolipid synthesis delays barrier recovery after acute perturbation. J Clin Invest 88:1338–1345

    Google Scholar 

  21. Holleran WM, Takagi Y, Menon GK, Jackson SM, Lee JM, Feingold KR, Elias PM (1994) Permeability barrier requirements regulate epidermal beta-glucocerebrosidase. J Lipid Res 35:905–912

    Google Scholar 

  22. Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A (1991) Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin?. J Invest Dermatol 96:523–526

    Google Scholar 

  23. Ishibashi M, Arikawa J, Okamoto R, Kawashima M, Takagi Y, Ohguchi K, Imokawa G (2003) Abnormal expression of the novel epidermal enzyme, glucosylceramide deacylase, and the accumulation of its enzymatic reaction product, glucosylsphingosine, in the skin of patients with atopic dermatitis. Lab Invest 83:397–408

    Google Scholar 

  24. Jin K, Higaki Y, Takagi Y, Higuchi K, Yada Y, Kawashima M, Imokawa G (1994) Analysis of beta-glucocerebrosidase and ceramidase activities in atopic and aged dry skin. Acta Derm Venereol 74:337–340

    Google Scholar 

  25. Kalinin AE, Kajava AV, Steinert PM (2002) Epithelial barrier function: assembly and structural features of the cornified cell envelope. Bioessays 24:789–800

    Google Scholar 

  26. Kusuda S, Cui CY, Takahashi M, Tezuka T (1998) Localization of sphingomyelinase in lesional skin of atopic dermatitis patients. J Invest Dermatol 111:733–738

    Google Scholar 

  27. Macheleidt O, Kaiser HW, Sandhoff K (2002) Deficiency of epidermal protein-bound omega-hydroxyceramides in atopic dermatitis. J Invest Dermatol 119:166–173

    Google Scholar 

  28. Matsumoto M, Sugiura H, Uehara M (2000) Skin barrier function in patients with completely healed atopic dermatitis. J Dermatol Sci 23:178–182

    Google Scholar 

  29. Matsumoto M, Umemoto N, Sugiura H, Uehara M (1999) Difference in ceramide composition between “dry” and “normal” skin in patients with atopic dermatitis. Acta Derm Venereol 79:246–247

    Google Scholar 

  30. Motta S, Monti M, Sesana S, Caputo R, Carelli S, Ghidoni R (1993) Ceramide composition of the psoriatic scale. Biochim Biophys Acta 1182:147–151

    Google Scholar 

  31. Motta S, Monti M, Sesana S, Mellesi L, Ghidoni R, Caputo R (1994) Abnormality of water barrier function in psoriasis. Role of ceramide fractions. Arch Dermatol 130:452–456

    Google Scholar 

  32. Norlén L, Nicander I, Lundh Rozell B, Ollmar S, Forslind B (1999) Inter- and intraindividual differences in human stratum corneum lipid content related to physical parameters of skin barrier function in vivo. J Invest Dermatol 112:72–77

    Google Scholar 

  33. Ohnishi Y, Okino N, Ito M, Imayama S (1999) Ceramidase activity in bacterial skin flora as a possible cause of ceramide deficiency in atopic dermatitis. Clin Diagn Lab Immunol 6:101–104

    Google Scholar 

  34. Ponec M, Weerheim A (1990) Retinoids and lipid changes in keratinocytes. Methods Enzymol 190:30–41

    Google Scholar 

  35. Ponec M, Weerheim A, Lankhorst P, Wertz P (2003) New acylceramide in native and reconstructed epidermis. J Invest Dermatol 120:581–588

    Google Scholar 

  36. Raith K, Neubert R (2000) Liquid chromatography-electrospray mass spectrometry and tandem mass spectrometry of ceramides. Anal Chim Acta 403:295–303

    Google Scholar 

  37. Raith K, Zellmer S, Lasch J, Neubert R (2000) Profiling of human stratum corneum ceramides by liquid chromatography-electrospray mass spectrometry. Anal Chim Acta 418:167–173

    Google Scholar 

  38. Robson KJ, Stewart ME, Michelsen S, Lazo ND, Downing DT (1994) 6-Hydroxy-4-sphingenine in human epidermal ceramides. J Lipid Res 35:2060–2068

    Google Scholar 

  39. Rogers J, Harding C, Mayo A, Banks J, Rawlings A (1996) Stratum corneum lipids: the effect of ageing and the seasons. Arch Dermatol Res 288:765–770

    Article  CAS  PubMed  Google Scholar 

  40. Signorelli P, Hannun YA (2002) Analysis and quantitation of ceramide. Methods Enzymol 345:275–294

    Google Scholar 

  41. Stewart ME, Downing DT (1999) A new 6-hydroxy-4-sphingenine-containing ceramide in human skin. J Lipid Res 40:1434–1439

    Google Scholar 

  42. Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F, Suzuki A, Elias PM, Holleran WM, Hamanaka S (2000) Epidermal sphingomyelins are precursors for selected stratum corneum ceramides. J Lipid Res 41:2071–2082

    Google Scholar 

  43. Vietzke JP, Brandt O, Abeck D, Rapp C, Strassner M, Schreiner V, Hintze U (2001) Comparative investigation of human stratum corneum ceramides. Lipids 36:299–304

    Google Scholar 

  44. Weerheim A, Ponec M (2001) Determination of stratum corneum lipid profile by tape stripping in combination with high-performance thin-layer chromatography. Arch Dermatol Res 293:191–199

    Article  CAS  PubMed  Google Scholar 

  45. Wertz PW, Madison KC, Downing DT (1989) Covalently bound lipids of human stratum corneum. J Invest Dermatol 92:109–111

    Google Scholar 

  46. Wertz PW, Miethke MC, Long SA, Strauss JS, Downing DT (1985) The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol 84:410–412

    Google Scholar 

  47. Yamamoto A, Serizawa S, Ito M, Sato Y (1991) Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res 283:219–223

    Google Scholar 

  48. Zellmer S, Lasch J (1997) Individual variation of human plantar stratum corneum lipids, determined by automated multiple development of high-performance thin-layer chromatography plates. J Chromatogr B Biomed Sci Appl 691:321–329

    Google Scholar 

Download references

Acknowledgements

The authors gratefully acknowledge financial support from the Kultusministerium Sachsen-Anhalt, project no. 3364A/0021L. The authors thank Manuela Woigk for excellent laboratory assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Johannes Wohlrab.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Farwanah, H., Raith, K., Neubert, R.H.H. et al. Ceramide profiles of the uninvolved skin in atopic dermatitis and psoriasis are comparable to those of healthy skin. Arch Dermatol Res 296, 514–521 (2005). https://doi.org/10.1007/s00403-005-0551-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00403-005-0551-2

Keywords

Navigation