Top

Published in:

Open Access 19-07-2022 | Atopic Dermatitis | Original Research

Efficacy of Pseudo-Ceramide-Containing Steroid Lamellar Cream in Patients with Mild to Moderate Atopic Dermatitis: A Randomized, Double-Blind Study

Authors: Keita Okoshi, Yoshinori Kinugasa, Shotaro Ito, Takuji Kume, Tsuyoshi Seki, Takahiro Nishizaka, Joji Okada, Hiromitsu Kawada, Azumi Nagasawa, Makoto Iijima, Masatoshi Abe, Osamu Nemoto

Published in: Dermatology and Therapy | Issue 8/2022

Abstract

Introduction

Atopic dermatitis (AD) is a chronic inflammatory skin disorder involving decreased barrier function of the stratum corneum. This decrease, caused by a reduction in ceramide, the primary component of intercellular lipids in the stratum corneum, leads to a disturbance in the lamellar structure.

Methods

We developed a formulation (test cream) containing a steroid and synthetic pseudo-ceramide (SLE: N-(3-hexadecyloxy-2-hydroxypropyl)-N-2-hydroxyethyl hexadecanamide) that forms a lamellar structure on the skin after its application and drying. The formulation or control cream (a formulation containing a steroid but not pseudo-ceramide that does not form a lamellar structure) was applied twice daily for 2 weeks to the lesional area of 34 participants with mild to moderate AD symptoms.

Results

The test cream showed a periodic structure with an interface space of approximately 8.2 nm in transmission electron microscopy and small- and wide-angle X-ray scattering, similar to the lamellar structure in the human stratum corneum. In the double-blind test, the anti-inflammatory effects of the test cream (n = 17) were comparable to those of the control cream (n = 17). In the test cream group, a significant increase in the stratum corneum moisture content (p < 0.01) and significant decrease in transepidermal water loss (p < 0.05) were observed at weeks 1 and 2 after application compared with those before application. No such change was observed in the control group.

Conclusion

The results indicate that, even with a relatively short application period of 2 weeks, the test cream not only suppressed inflammation of the lesional area, but also improved the inherent barrier function of the stratum corneum, suggesting its potential as a treatment option for patients with AD.

Saeki H, Furue M, Furukawa F, Hide M, Ohtsuki M, Katayama I, et al. Guidelines for management of atopic dermatitis. J Dermatol. 2009;36:563–77. https://doi.org/10.1111/j.1346-8138.2009.00706.x.CrossRefPubMed

Katayama I, Kohno Y, Akiyama K, Ikezawa Z, Kondo N, Tamaki K, et al. Japanese guideline for atopic dermatitis. Allergol Int. 2011;60:205–20. https://doi.org/10.2332/allergolint.11-rai-0333.CrossRefPubMed

Lodén M. Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders. Am J Clin Dermatol. 2003;4:771–88. https://doi.org/10.2165/00128071-200304110-00005.CrossRefPubMed

Tagami H, Ohi M, Iwatsuki K, Kanamaru Y, Yamada M, Ichijo B. Evaluation of the skin surface hydration in vivo by electrical measurement. J Invest Dermatol. 1980;75:500–7. https://doi.org/10.1111/1523-1747.ep12524316.CrossRefPubMed

Kikuchi K, Tagami H. Japanese Cosmetic Scientist Task Force for Skin Care of Atopic Dermatitis. Noninvasive biophysical assessments of the efficacy of a moisturizing cosmetic cream base for patients with atopic dermatitis during different seasons. Br J Dermatol. 2008;158:969–78. https://doi.org/10.1111/j.1365-2133.2008.08478.x.CrossRefPubMed

Imokawa G, Abe A, Jin K, Higaki Y, Kawashima M, Hidano A. Decreased level of ceramides in stratum corneum of atopic dermatitis: an etiologic factor in atopic dry skin? J Invest Dermatol. 1991;96:523–6. https://doi.org/10.1111/1523-1747.ep12470233.CrossRefPubMed

Kobayashi T, Glatz M, Horiuchi K, Kawasaki H, Akiyama H, Kaplan DH, et al. Dysbiosis and Staphylococcus aureus colonization drives inflammation in atopic dermatitis. Immunity. 2015;42:756–66. https://doi.org/10.1016/j.immuni.2015.03.014.CrossRefPubMedPubMedCentral

Van Smeden J, Janssens M, Gooris GS, Bouwstra JA. The important role of stratum corneum lipids for the cutaneous barrier function. Biochim Biophys Acta. 2014;1841:295–313. https://doi.org/10.1016/j.bbalip.2013.11.006.CrossRefPubMed

Elias PM, Goerke J, Friend DS. Mammalian epidermal barrier layer lipids: composition and influence on structure. J Invest Dermatol. 1977;69:535–46. https://doi.org/10.1111/1523-1747.ep12687968.CrossRefPubMed

10.

Fartasch M, Bassukas ID, Diepgen TL. Disturbed extruding mechanism of lamellar bodies in dry non-eczematous skin of atopics. Br J Dermatol. 1992;127:221–7. https://doi.org/10.1111/j.1365-2133.1992.tb00118.x.CrossRefPubMed

11.

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;130:2511–4. https://doi.org/10.1038/jid.2010.161.CrossRefPubMed

12.

van Smeden J, Janssens M, Kaye EC, Caspers PJ, Lavrijsen AP, Vreeken RJ, et al. The importance of free fatty acid chain length for the skin barrier function in atopic eczema patients. Exp Dermatol. 2014;23:45–52. https://doi.org/10.1111/exd.12293.CrossRefPubMed

13.

Janssens M, van Smeden J, Gooris GS, Bras W, Portale G, Caspers PJ, et al. Lamellar lipid organization and ceramide composition in the stratum corneum of patients with atopic eczema. J Invest Dermatol. 2011;131:2136–8. https://doi.org/10.1038/jid.2011.175.CrossRefPubMed

14.

Janssens M, van Smeden J, Gooris GS, Bras W, Portale G, Caspers PJ, et al. Increase in short-chain ceramides correlates with an altered lipid organization and decreased barrier function in atopic eczema patients. J Lipid Res. 2012;53:2755–66. https://doi.org/10.1194/jlr.P030338.CrossRefPubMedPubMedCentral

15.

Yamamoto A, Serizawa S, Ito M, Sato Y. Stratum corneum lipid abnormalities in atopic dermatitis. Arch Dermatol Res. 1991;283:219–23. https://doi.org/10.1007/BF01106105.CrossRefPubMed

16.

Di Nardo A, Wertz P, Giannetti A, Seidenari S. Ceramide and cholesterol composition of the skin of patients with atopic dermatitis. Acta Derm Venereol. 1998;78:27–30. https://doi.org/10.1080/00015559850135788.CrossRefPubMed

17.

Imokawa G, Ishida K. Role of ceramide in the barrier function of the stratum corneum, implications for the pathogenesis of atopic dermatitis. J Clin Exp Dermatol Res. 2014;5:1000206.CrossRef

18.

Berardesca E, Barbareschi M, Veraldi S, Pimpinelli N. Evaluation of efficacy of a skin lipid mixture in patients with irritant contact dermatitis, allergic contact dermatitis or atopic dermatitis: a multicenter study. Contact Dermatitis. 2001;45:280–5. https://doi.org/10.1034/j.1600-0536.2001.450505.x.CrossRefPubMed

19.

Chamlin SL, Frieden IJ, Fowler A, Williams M, Kao J, Sheu M, et al. Ceramide-dominant, barrier-repair lipids improve childhood atopic dermatitis. Arch Dermatol. 2001;137:1110–2.PubMed

20.

Seghers AC, Cai SC, Ho MS, Giam YC, Tan L, Grönhagen CM, et al. Evaluation of a pseudoceramide moisturizer in patients with mild-to-moderate atopic dermatitis. Dermatol Ther (Heidelb). 2014;4:83–92. https://doi.org/10.1007/s13555-014-0048-z.CrossRef

21.

Simpson E, Böhling A, Bielfeldt S, Bosc C, Kerrouche N. Improvement of skin barrier function in atopic dermatitis patients with a new moisturizer containing a ceramide precursor. J Dermatolog Treat. 2013;24:122–5. https://doi.org/10.3109/09546634.2012.713461.CrossRefPubMed

22.

Imokawa G, Akasaki S, Kawamata A, Yano S, Takaishi N. Water retaining function in the stratum corneum and its recovery properties by synthetic pseudoceramides. J Soc Cosmet Chem. 1989;40:273–85.

23.

Hata M, Tokura Y, Takigawa M, Tamura Y, Imokawa G. Efficacy of using pseudoceramide-containing cream for the treatment of atopic dry skin in comparison with urea cream. Nishinihon J Dermatol. 2002;64:606–11. https://doi.org/10.2336/nishinihonhifu.64.606.CrossRef

24.

Matsuki H, Kiyokane K, Matsuki T, Sato S, Imokawa G. Recharacterization of the nonlesional dry skin in atopic dermatitis through disrupted barrier function. Exog Dermatol. 2004;3:282–92. https://doi.org/10.1159/000091909.CrossRef

25.

Matsuki H, Kiyokane K, Matsuki T, Sato S, Imokawa G. Reevaluation of the importance of barrier dysfunction in the nonlesional dry skin of atopic dermatitis patients through the use of two barrier creams. Exog Dermatol. 2004;3:293–302. https://doi.org/10.1159/000091910.CrossRef

26.

Saeki H, Furue M, Furukawa F, et al. Guidelines for management of atopic dermatitis. J Dermatol. 2009;36:563–77. https://doi.org/10.1111/j.1346-8138.2009.00706.x.CrossRefPubMed

27.

Eichenfield LF, Tom WL, Berger TG, et al. Guideline of care for the management of atopic dermatitis. Section 2. Management and treatment of atopic dermatitis with topical therapies. J Am Acad Dermatol. 2014;71:116–32.CrossRef

28.

Orita M, Uchiyama M, Hanamoto T, Yamashita O, Naitou S, Takeuchi K, et al. Formation of pseudo-intercellular lipids membrane on the skin surface by the alpha-gel holding a large amount of water. J Soc Cosmet Chem Jpn. 2012;46:25–32. https://doi.org/10.5107/sccj.46.25.CrossRef

29.

Yamaguchi M, Takahashi M, Harusawa F, Fukushima S. Mechanism of stabillization by cetyl alcohol for oil in water cream. J Soc Cosmet Chem Jpn. 1978;12:16–22. https://doi.org/10.5107/sccj1976.12.2_16.CrossRef

30.

Pilgram GS, Bouwstra JA. Stratum corneum lipid organization in vitro and in vivo as assessed by diffraction methods. In: Forslind B, Lindberg M, editors. Skin, hair, and nails: structure and function. New York: Marcel Dekker; 2004.

31.

Hatta I, Nakanishi K, Ohta N. Structure and phase transitions of intercellular lipid assembly in stratum corneum. Netsu Sokutei. 2004;34:159–66.

32.

Ohta N, Ban S, Tanaka H, Nakata S, Hatta I. Swelling of intercellular lipid lamellar structure with short repeat distance in hairless mouse stratum corneum as studied by X-ray diffraction. Chem Phys Lipids. 2003;123:1–8. https://doi.org/10.1016/s0009-3084(02)00126-3.CrossRefPubMed

33.

Junker JP, Kamel RA, Caterson EJ, Eriksson E. Clinical impact upon wound healing and inflammation in moist, wet, and dry environments. Adv Wound Care. 2013;2:348–56. https://doi.org/10.1089/wound.2012.0412.CrossRef

34.

Zhai H, Maibach HI. Effect of occlusion and semi-occlusion on experimental skin wound healing: a reevaluation. Wounds. 2007;19:270–6.PubMed

35.

Zehrer CL, Holm D, Solfest SE, Walters SA. A comparison of the in vitro moisture vapour transmission rate and in vivo fluid-handling capacity of six adhesive foam dressings to a newly reformulated adhesive foam dressing. Int Wound J. 2014;11:681–90. https://doi.org/10.1111/iwj.12030.CrossRefPubMed

36.

Feingold KR, Denda M. Regulation of permeability barrier homeostasis. Clin Dermatol. 2012;30:263–8. https://doi.org/10.1016/j.clindermatol.2011.08.008.CrossRefPubMed

37.

Schmitt J, von Kobyletzki L, Svensson A, Apfelbacher C. Efficacy and tolerability of proactive treatment with topical corticosteroids and calcineurin inhibitors for atopic eczema: systematic review and meta-analysis of randomized controlled trials. Br J Dermatol. 2011;164:415–28. https://doi.org/10.1111/j.1365-2133.2010.10030.x.CrossRefPubMed

38.

Murota H, Takeuchi S, Sugaya M, Tanioka M, Onozuka D, Hagihara A, et al. Characterization of socioeconomic status of Japanese patients with atopic dermatitis showing poor medical adherence and reasons for drug discontinuation. J Dermatol Sci. 2015;79:279–87. https://doi.org/10.1016/j.jdermsci.2015.05.010.CrossRefPubMed

39.

Furue M, Onozuka D, Takeuchi S, Murota H, Sugaya M, Masuda K, et al. Poor adherence to oral and topical medication in 3096 dermatological patients as assessed by the Morisky Medication Adherence Scale-8. Br J Dermatol. 2015;172:272–5. https://doi.org/10.1111/bjd.13377.CrossRefPubMed

Title: Efficacy of Pseudo-Ceramide-Containing Steroid Lamellar Cream in Patients with Mild to Moderate Atopic Dermatitis: A Randomized, Double-Blind Study
Authors: Keita Okoshi
Yoshinori Kinugasa
Shotaro Ito
Takuji Kume
Tsuyoshi Seki
Takahiro Nishizaka
Joji Okada
Hiromitsu Kawada
Azumi Nagasawa
Makoto Iijima
Masatoshi Abe
Osamu Nemoto
Publication date: 19-07-2022
Publisher: Springer Healthcare
Keyword: Atopic Dermatitis
Published in: Dermatology and Therapy / Issue 8/2022
Print ISSN: 2193-8210
Electronic ISSN: 2190-9172
DOI: https://doi.org/10.1007/s13555-022-00766-2

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 8/2022

Update on the Management of Pediatric Psoriasis: An Italian Consensus

Patient Characteristics and Treatment Patterns in European Pediatric Patients with Psoriasis: A Real-World, Cross-Sectional Study

Efficacy of Bimekizumab and Other Biologics in Moderate to Severe Plaque Psoriasis: A Systematic Literature Review and a Network Meta-Analysis

A Systematic Literature Review of Economic Evaluations and Cost Studies of the Treatment of Psoriasis, Atopic Dermatitis, and Chronic Urticaria

Demographic and Clinical Factors Associated with Patient-Reported Remission in Psoriatic Arthritis

Burden of Moderate to Severe Atopic Dermatitis in Adults from France, Italy, and the UK: Patient-Reported Outcomes and Treatment Patterns

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials