REVIEW

The structure, function, and importance of

ceramides in skin and their use as therapeutic
agents in skin-care products
Matthew H. Meckfessel, PhD, and Staci Brandt, PA-C, MSMR, MBA
Fort Worth, Texas

Ceramides (CERs) are epidermal lipids that are important for skin barrier function. Much research has been
devoted to identifying the numerous CERs found in human skin and their function. Alterations in CER
content are associated with a number of skin diseases such as atopic dermatitis. Newer formulations of
skin-care products have incorporated CERs into their formulations with the goal of exogenously applying
CERs to help skin barrier function. CERs are a complex class of molecules and because of their growing
ubiquity in skin-care products, a clear understanding of their role in skin and use in skin-care products is
essential for clinicians treating patients with skin diseases. This review provides an overview of the
structure, function, and importance of skin CERs in diseased skin and how CERs are being used in skin-care
products to improve or restore skin barrier function. ( J Am Acad Dermatol http://dx.doi.org/10.1016/
j.jaad.2014.01.891.)

Key words: ceramide; epidermal repair; skin barrier; skin care; skin disease.

C eramides (CERs) are important structural

components of the epidermis, which plays
a key role in maintaining homeostasis of the
human body.1 Specifically, its outermost layer,
known as the stratum corneum, forms a barrier
between the external environment and the internal
body.2 This barrier function serves multiple
purposes including prevention of water loss and
protection from foreign insult. The structure of the
stratum corneum is often referred to as ‘‘brick and
mortar.’’3 The ‘‘bricks’’ are terminally differentiated
keratinocytes composed mostly of keratin filaments
and filaggrin.4 The ‘‘mortar’’ is composed of
intercellular lipids arranged into lamellar layers
consisting of CERs, free fatty acids, and cholesterol.
CERs are the predominant lipid comprising
approximately 50% of the intercellular lipid content
by mass.3 Stratum corneum lipids are essential for
maintaining skin barrier function and preventing
transepidermal water loss (TEWL). Disruptions or
damage to the stratum corneum can impair skin
barrier function and result in TEWL.
Abbreviations used:
CER:
CERSyn:
FLG:
ceramide
ceramide synthase
filaggrin gene
TEWL: transepidermal water loss
CERs have been added to newer cosmetic
products to improve skin barrier function and
exogenously replenish skin CERs. Of the stratum
corneum intercellular lipids, CERs are the most
effective at restoring barrier function and increasing
skin hydration.5 Different CERs have been incorpo-
rated into cosmetic formulations, but understanding
the differences between CERs used in formulations,
or even identifying CERs in formulations can be
complex. This is mostly because of an archaic
nomenclature system that is fundamentally flawed
based on current scientific evidence.6
The term ‘‘ceramide’’ may only be used in an
International Nomenclature of Cosmetic Ingredients
(INCI) name7 to designate CERs identified in a 1985

From Galderma Laboratories LP. Published online March 19, 2014.

Funded by Galderma Laboratories LP. 0190-9622/$36.00
Disclosure: Dr Meckfessel and Ms Brandt are employees of Ó 2014 by the American Academy of Dermatology, Inc.
Galderma Laboratories LP. http://dx.doi.org/10.1016/j.jaad.2014.01.891
Accepted for publication January 31, 2014.
Reprint requests: Matthew H. Meckfessel, PhD, Galderma
Laboratories LP, 14501 N Freeway, Fort Worth, TX 76177.
E-mail: matthew.meckfessel@galderma.com.

1
2 Meckfessel and Brandt J AM ACAD DERMATOL

article by Wertz et al.8 Newer more sensitive analy- chain length ranges from 14 to 32 carbons, but those
tical techniques have identified additional classes of greater than 20 carbons predominate.
CERs and CER species in human skin that were not
identified by Wertz et al.8 However, because of the SKIN CER PRODUCTION
archaic INCI nomenclature, these CERs may not CERs are produced via 2 different pathways: a de
be called ‘‘ceramides’’ on ingredient labels. Until novo pathway and a salvage pathway.13 The de
the INCI nomenclature is updated to reflect our novo pathway is the route of CER production
current understanding of in the skin.14,15 Serine and
CERs, identifying CERs as palmitoyl-coenzyme-A (CoA)
ingredients may continue to CAPSULE SUMMARY are condensed to make 3-keto
be challenging. dihydrosphingosine, which is
d Ceramides (CERs) are an important class
Because of their impor- converted into dihydrosphin-
of molecules necessary for skin barrier
tance in maintaining the skin gosine. Dihydrosphingosine
function, and changes in skin CER
barrier, much research has is N-acylated using fatty
content are associated with a number of
been focused on the roles of acetyl-CoA by CER synthase
diseases such as atopic dermatitis and
CERs in the stratum corneum (CERSyn) producing dihydro-
psoriasis.
in healthy and diseased CER. Dihydro-CER can be
skin and the use of CERs d CERs have been incorporated into skin- further modified through
as therapeutic agents for care product formulations, which aim to desaturation or hydroxylation
improving skin barrier func- restore skin barrier function through to produce the various other
tion. Understanding their role exogenous application of CERs. sphingoid bases found in
in skin and use in skin-care d It is important for clinicians to have an skin CERs. CERSyn can also
products may be important for understanding of the importance of this N-acylate sphingoid bases
clinicians as CERs become class of molecules, and how they are other than dihydrosphingo-
more ubiquitous. The aim of being incorporated into skin-care sine, such as sphingosine. Six
this review is to discuss the products. CERSyns have been identified
structure, function, and impor- in human beings.13 They differ
tance of skin CERs in diseased in their preference for fatty
skin and how CERs are being used in skin-care products acyl-CoA length and their expression is tissue specific.
to improve or restore skin barrier function. De novo skin CER synthesis occurs in the supra-
basal layers of the epidermis in the endoplasmic
SKIN CER STRUCTURE reticulum.14,16 CERSyn3 is up-regulated in differen-
The basic CER is composed of a sphingoid base tiated keratinocytes and has a preference for longer
conjugated to a fatty acid via an amide bond (Fig 1). chained fatty acyl-CoA molecules, which correlates
However, the composition of CERs within the human to higher length CERs in the stratum corneum.17
stratum corneum is very heterogeneous. The number Newly produced CERs are transported to the Golgi
of CER classes identified in human skin has grown to apparatus where they are either glucosylated or
12, and differ from one another based on the converted to sphingomyelin.14 Glucosyl-CERs and
composition of the head group or esterification of sphingomyelins are transported through the Golgi
the fatty acid (Fig 2).9,10 There are currently 4 different apparatus into secretory vesicles that accumulate
sphingoid bases and 3 different types of fatty acids and increase in number as keratinocytes differentiate
identified thus far. Within these 12 classes, chain through the stratum corneum (Fig 3). When the
length of the sphingoid base or fatty acid differentia- keratinocytes reach the boundary between the
tes specific CERs. The number of CERs within human stratum granulosum and the stratum corneum, the
skin is extensive; over 340 CER species have been secretory vesicles fuse with the plasma membrane
identified within the forearm stratum corneum.11 and deposit their content into the intercellular space
The length of CERs within human skin is quite of the stratum corneum. Once deposited into the
variable.9 Nonhydroxy fatty acid sphingosine CERs stratum corneum, glucosyl-CERs and sphingomye-
analyzed from human cheek skin and forearm skin lins are processed back to CERs by b-glucocerebro-
contain 33 to 52 total carbon atoms. However, CER sidase and sphingomyelinase, respectively.18-20
species with at least 42 carbons are more abundant in
either skin sample compared with smaller CER SKIN CERS IN SKIN DISEASES
species less than 42 carbons in size. A propensity CERSyn
for longer chain length is also reflected in stratum A study conducted in mice showed that CERSyn3
corneum free fatty acids.12 Epidermal free fatty acid was essential for survival.21 Mice deficient in
J AM ACAD DERMATOL
Fig 1. Basic ceramide (CER) structure. A fatty acid is conjugated to a sphingoid base to make
a CER.
CERSyn3 died shortly after birth as a result of TEWL.
Cultured skin from newborn mice was also more
susceptible to colonization by Candida albicans,
underscoring the importance of skin barrier function
to protect against foreign insult. Analysis of CER
composition in CERSyn3-deficient mice revealed
complete loss of long-chain CERs containing acyl
moieties greater than 26 carbons in length.
Gaucher disease
Gaucher disease is a rare inherited disorder
caused by a deficiency in b-glucocerebrosidase
with a range of clinical severity ranging from
lethal to asymptomatic.22,23 Type 2 Gaucher
disease is characterized by ichthyosiform skin
and diseased skin is marked by an elevated
glucosyl-CER to CER ratio and ultrastructural
abnormalities such as immature and unprocessed
lamellar bodies.24,25 In vitro and in vivo experiments
in mice have confirmed the importance of a
functional b-glucocerebrosidase in maintaining the
skin barrier.19,20 Skin from b-glucocerebrosidase
knockout mice, mice treated with a b-glucocerebro-
sidase inhibitor, and cultured mouse skin treated
with a b-glucocerebrosidase inhibitor phenocopies
type 2 Gaucher diseased skin.
Psoriasis
Abnormal CER composition in psoriasis plaques is
associated with disrupted skin barrier function and
an increase in TEWL.26 In particular, long-chain CERs
Meckfessel and Brandt 3
containing ester-linked fatty acids and CERs
containing phytosphingosine were reduced in
psoriatic skin compared with normal-appearing
skin.27 However, the total amount of CERs in
psoriatic skin was unchanged compared with
normal-appearing skin. Psoriatic skin has also been
found to have reduced prosaposin messenger RNA
expression and protein levels.28 Prosaposin is
processed into saposin, a nonenzymatic protein
required for hydrolysis of sphingolipids, including
postsecretory glucosyl-CERs in the stratum
corneum.29 Reduced levels of sphingomyelinase
have also been observed in psoriatic skin compared
with nonlesional skin.28 Taken together these data
indicate that CER composition, and not necessarily
the amount of CERs, and proper processing
of CER precursors, such as glucosyl-CERs and
sphingomyelin, is required for proper skin barrier
function.
Atopic dermatitis
Atopic dermatitis is a common skin disease
affecting up to 18% of the US pediatric population
and is characterized by dry skin, pruritus, increased
TEWL, and decreased skin barrier function.30,31
Atopic dermatitis is strongly associated with
mutations in the filaggrin gene (FLG), but these
mutations are not the sole causative factor for atopic
dermatitis as barrier function is compromised in all
patients with atopic dermatitis irrespective of FLG
genotype.32-35
4 Meckfessel and Brandt
Fig 2. Different classes of ceramides (CERs). Three classes of fatty acids and 4 classes of
sphingoid bases give rise to the 12 different classes of CERs. Varying chain length of the fatty
acid and sphingoid base moieties differentiate individual CER species.
Skin CER levels are significantly reduced in
atopic dermatitis lesional skin compared with
age-controlled healthy skin.36 Reduced levels of
CERs are also observed in nonlesional skin of
patients with atopic dermatitis. Specifically CER 1, a
long-chained CER containing an ester-linked fatty
acid (Fig 4), was the most reduced CER in lesional
and nonlesional skin.
The composition of CERs in atopic dermatitis skin
is also different compared with normal-appearing
skin.37 For example, levels of CERs containing
an ester-linked fatty acid and sphingosine were
significantly lower in atopic dermatitis skin
compared with healthy skin, whereas levels of
CERs containing an a-hydroxy fatty acid and
sphingosine were significantly higher in atopic
dermatitis skin compared with healthy skin. Within
each class of CERs, atopic dermatitis was associated
with reduced levels of larger CERs ([50 carbons)
and elevated levels of smaller CERs (\40 carbons).
In a study of nonlesional skin in patients with
atopic eczema, small CERs of 34 carbons were
significantly increased compared with normal-
appearing control skin.38 Significant differences in
CER classes were also observed between patients
with atopic eczema and healthy control subjects.
J AM ACAD DERMATOL
However, there was no significant difference in
total CERs, which is different from previously
reported.36,38 The decrease in chain length was
more strongly associated with disruption in skin
barrier function than alterations in CER class
composition.38 Decreasing CER size was correlated
with altered intercellular lipid organization,
increased TEWL, disease severity, and levels of
natural moisturizing factor. Interestingly, CER size
did not correlate with FLG mutation genotypes. This
suggests that although FLG mutations strongly
correlate with atopic eczema/atopic dermatitis,
changes in CER size may play a more important
role in the pathogenesis than previously appreciated.
Additional variations in proteins responsible for
maintaining stratum corneum CER homeostasis have
been associated with atopic dermatitis.39,40 Similar to
what has been observed with psoriasis, levels of
prosaposin are significantly decreased in atopic
dermatitis skin.39 The authors suggest that reduced
prosaposin, and subsequent processing into saposin,
may contribute to lower CER levels in atopic dermatitis
skin through suppression of glucosyl-CER and
sphingomyelin processing in the stratum corneum.
Increased expression and activity of sphingomyelin
deacylase is also associated with atopic dermatitis.40
J AM ACAD DERMATOL Meckfessel and Brandt 5

Fig 3. Overview of ceramide (CER) synthesis in skin. A, CER synthesis begins in the stratum
basale. CERs are synthesized de novo in the endoplasmic reticulum by conjugation of a fatty acid to
a sphingoid base. B, CERs are glucosylated or converted to sphingomyelin (SM) in the Golgi
apparatus and packaged into secretory vesicles. The number of vesicles increases as keratinocytes
differentiate as seen in the stratum spinosum layer. C, Vesicles exocytose glucosyl-CERs and
sphingomyelins into the extracellular space where b-glucocerebrosidase and sphingomyelinase
convert them back into CERs, respectively. D, CERs, along with free fatty acids and cholesterol,
organize into lamellar layers in the intercellular space of corneocytes in the stratum corneum.

Sphingomyelin deacylase is an enzyme that is able
to deacylate glucosyl-CER and sphingomyelin to
produce glucosyl sphingosine and sphingosyl-
phosphorylcholine, respectively. Sphingomyelin
deacylase competes with b-glucocerebrosidase and
sphingomyelinase for glucosyl-CER and sphingo-
myelin substrates. Thus, elevated sphingomyelin
deacylase levels may contribute to reduced CER levels
and altered skin barrier function in patients with atopic
dermatitis.
CERS AS THERAPEUTIC AGENTS
Hydroxypalmitoyl sphinganine
Hydroxypalmitoyl sphinganine is a CER containing
a hydroxyl fatty acid acylated to dihydrosphingosine
(Fig 4). It is similar to CER 5, which contains a
6 Meckfessel and Brandt
Fig 4. The molecular structures of 3 different ceramides (CERs) that have been used in
cosmetic formulations. Sphingolipid E is an example of a pseudo-CER with skin barrier
restoring properties that are similar to CERs.
sphingosine instead of dihydrosphingosine.41
Addition of hydroxypalmitoyl sphinganine to growth
media of cultured human reconstructed skin resulted
in an increase of CERs 1, 2, and 3.42 The increase of
CERs 1, 2, and 3 was a result of processing and
transformation of hydroxypalmitoyl sphinganine into
these CERs, and not caused by de novo CER synthesis.
Thus, in vitro experiments demonstrate that the
addition of hydroxypalmitoyl sphinganine can induce
production of endogenous CERs and increase total
CER content in human reconstructed skin.
Hydroxypalmitoyl sphinganine has been formu-
lated into moisturizers (Cetaphil RestoraDerm Skin
Restoring Moisturizer [Galderma Laboratories, LP,
Fort Worth, TX] and Cetaphil DermaControl
Moisturizer SPF 30) and a body wash (Cetaphil
RestoraDerm Body Wash). Clinical studies have
shown these products are able to improve skin
hydration, reduce TEWL, and increase stratum
corneum CERs in patients with atopic dermatitis or
who are being treated with topical tretinoin.43-46
CERs 1 and 3
CER 1 contains a long-chain ester-linked fatty acid
acylated to sphingosine (Fig 4).41 As discussed
earlier, CERs with higher number carbons, such as
CER 1, are important for maintaining skin
barrier function. CER 3 contains a 24-carbon fatty
acid acylated to phytosphingosine (Fig 4). One study
demonstrated that CERs 1 and 3 acted synergistically
in an emulsion to improve skin hydration and
reduce TEWL in skin treated with sodium lauryl
sulfate.47
J AM ACAD DERMATOL
CERs 1 and 3 have been formulated into several
commercial lotions, creams, and moisturizers
(eg, Eucerin Smoothing Repair Dry Skin Lotion
[Beiersdorf, Inc, Hamburg, Germany], Eucerin
Eczema Relief Body Creme, CeraVe Moisturizing
Lotion [Valeant Pharmaceuticals Internationial, Inc,
Bridgewater, NJ], CeraVe Suncare Sunscreen Face
SPF 30). Clinical studies in patients with atopic
skin have demonstrated the effectiveness of these
products at improving skin hydration and skin
barrier function.48,49
Pseudo-CERs
Pseudo-CERs are chemical entities that are
structurally similar to CERs, however, they may
have differences such as lacking a sphingoid base
or having a tertiary amine group (Fig 4).50 Although
they are not true CERs, they are still able to restore
barrier function in damaged skin.50,51 Barrier
function improved in sodium lauryl sulfate or
acetone/ether-treated forearm skin after application
of pseudo-CERs.50 Rats with an essential fatty acid
deficiency experience progressive barrier defects
because of an alteration of CERs.51 Treatment with
pseudoacyl-CER was able to improve barrier
function in essential fatty acidedeficiency rats
indicating that these CER-like compounds can
function in a similar manner to true CERs. Similar
to CERs, pseudo-CERs have also been incorporated
into commercially available skin-care formulations
(eg, Kao Men’s Biore Double Moisture Cream
[Kao Corporation, Tokyo, Japan] and L’Actua Deep
Harmonize Cream [Ajinomoto Health Supply, Tokyo,
Japan]). Of note, however, is that these ingredients
J AM ACAD DERMATOL
are primarily found in formulations available in Asian
markets.
Conclusion
CERs are a complex class of lipids that are
necessary for maintaining skin barrier function.
Alterations in CER levels or composition are associ-
ated with diseased skin, such as atopic dermatitis and
psoriasis. Newer skin-care formulations have begun
to incorporate CERs; exogenously applied CERs may
help to restore skin CER levels, which may help
improve skin barrier function through increased skin
hydration and reduced TEWL. As more CERs are
identified through continued research, it may be
possible to specifically formulate skin-care products
with different CERs for a specific disease or condition.
REFERENCES
1. Elias PM, Menon GK. Structural and lipid biochemical
correlates of the epidermal permeability barrier. Adv Lipid
Res 1991;24:1-26.
2. Del Rosso JQ, Levin J. Clinical relevance of maintaining the
structural and functional integrity of the stratum corneum: why
is it important to you? J Drugs Dermatol 2011;10(Suppl):S5-12.
3. Harding CR. The stratum corneum: structure and function in
health and disease. Dermatol Ther 2004;17(Suppl):6-15.
4. Proksch E, Brandner JM, Jensen JM. The skin: an indispensable
barrier. Exp Dermatol 2008;17:1063-72.
5. Imokawa G, Akasaki S, Hattori M, Yoshizuka N. Selective
recovery of deranged water-holding properties by stratum
corneum lipids. J Invest Dermatol 1986;87:758-61.
6. Farwick M, Lersch P, Santonnat B, Korevaar K, Rawlings AV.
Developments in ceramide identification, synthesis, function,
and nomenclature. Cosmet Toiletries 2009;124:63-72.
7. European CommissioneEnterprise and Industry Directorate
General Consumer Goods. INCIenomenclature conventions.
2006. Available from: URL:http://www.surfatech.com/pdfs/
INCI_Names.pdf. Accessed October 25, 2013.
8. Wertz PW, Miethke MC, Long SA, Strauss JS, Downing DT. The
composition of the ceramides from human stratum corneum
and from comedones. J Invest Dermatol 1985;84:410-2.
9. Masukawa Y, Narita H, Sato H, Naoe A, Kondo N, Sugai Y, et al.
Comprehensive quantification of ceramide species in human
stratum corneum. J Lipid Res 2009;50:1708-19.
10. van Smeden J, Hoppel L, van der Heijden R, Hankemeier T,
Vreeken RJ, Bouwstra JA. LC/MS analysis of stratum corneum
lipids: ceramide profiling and discovery. J Lipid Res 2011;52:
1211-21.
11. 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;49:1466-76.
12. Norlen L, Nicander I, Lundsjo A, Cronholm T, Forslind B. A new
HPLC-based method for the quantitative analysis of inner
stratum corneum lipids with special reference to the free fatty
acid fraction. Arch Dermatol Res 1998;290:508-16.
13. Mullen TD, Hannun YA, Obeid LM. Ceramide synthases
at the centre of sphingolipid metabolism and biology.
Biochem J 2012;441:789-802.
14. Mizutani Y, Mitsutake S, Tsuji K, Kihara A, Igarashi Y. Ceramide
biosynthesis in keratinocyte and its role in skin function.
Biochimie 2009;91:784-90.
Meckfessel and Brandt 7
15. Merrill AH Jr. De novo sphingolipid biosynthesis: a necessary,
but dangerous, pathway. J Biol Chem 2002;277:25843-6.
16. Levy M, Futerman AH. Mammalian ceramide synthases. IUBMB
Life 2010;62:347-56.
17. Mizutani Y, Kihara A, Chiba H, Tojo H, Igarashi Y.
2-Hydroxy-ceramide synthesis by ceramide synthase
family: enzymatic basis for the preference of FA chain
length. J Lipid Res 2008;49:2356-64.
18. Uchida Y, Hara M, Nishio H, Sidransky E, Inoue S, Otsuka F,
et al. Epidermal sphingomyelins are precursors for selected
stratum corneum ceramides. J Lipid Res 2000;41:2071-82.
19. Holleran WM, Takagi Y, Menon GK, Legler G, Feingold KR,
Elias PM. Processing of epidermal glucosylceramides is
required for optimal mammalian cutaneous permeability
barrier function. J Clin Invest 1993;91:1656-64.
20. Holleran WM, Ginns EI, Menon GK, Grundmann JU, Fartasch M,
McKinney CE, et al. Consequences of beta-glucocerebrosidase
deficiency in epidermis: ultrastructure and permeability barrier
alterations in Gaucher disease. J Clin Invest 1994;93:1756-64.
21. Jennemann R, Rabionet M, Gorgas K, Epstein S, Dalpke A,
Rothermel U, et al. Loss of ceramide synthase 3 causes lethal
skin barrier disruption. Hum Mol Genet 2012;21:586-608.
22. Sidransky E. Gaucher disease: insights from a rare Mendelian
disorder. Discov Med 2012;14:273-81.
23. Grabowski GA. Gaucher disease and other storage disorders.
Hematology Am Soc Hematol Educ Program 2012;2012:13-8.
24. Sidransky E, Fartasch M, Lee RE, Metlay LA, Abella S, Zimran A,
et al. Epidermal abnormalities may distinguish type 2 from
type 1 and type 3 of Gaucher disease. Pediatr Res 1996;39:
134-41.
25. Chan A, Holleran WM, Ferguson T, Crumrine D, Goker-Alpan O,
Schiffmann R, et al. Skin ultrastructural findings in type 2
Gaucher disease: diagnostic implications. Mol Genet Metab
2011;104:631-6.
26. Motta S, Monti M, Sesana S, Mellesi L, Ghidoni R, Caputo R.
Abnormality of water barrier function in psoriasis: role of
ceramide fractions. Arch Dermatol 1994;130:452-6.
27. Motta S, Monti M, Sesana S, Caputo R, Carelli S, Ghidoni R.
Ceramide composition of the psoriatic scale. Biochim Biophys
Acta 1993;1182:147-51.
28. Alessandrini F, Stachowitz S, Ring J, Behrendt H. The level of
prosaposin is decreased in the skin of patients with psoriasis
vulgaris. J Invest Dermatol 2001;116:394-400.
29. Doering T, Holleran WM, Potratz A, Vielhaber G, Elias PM,
Suzuki K, et al. Sphingolipid activator proteins are required for
epidermal permeability barrier formation. J Biol Chem 1999;
274:11038-45.
30. Shaw TE, Currie GP, Koudelka CW, Simpson EL. Eczema
prevalence in the United States: data from the 2003
National Survey of Children’s Health. J Invest Dermatol 2011;
131:67-73.
31. Sugarman JL. The epidermal barrier in atopic dermatitis.
Semin Cutan Med Surg 2008;27:108-14.
32. Flohr C, England K, Radulovic S, McLean WH, Campbel LE,
Barker J, et al. Filaggrin loss-of-function mutations are
associated with early-onset eczema, eczema severity and
transepidermal water loss at 3 months of age. Br J Dermatol
2010;163:1333-6.
33. O’Regan GM, Kemperman PM, Sandilands A, Chen H,
Campbell LE, Kroboth K, et al. Raman profiles of the
stratum corneum define 3 filaggrin genotype-determined
atopic dermatitis endophenotypes. J Allergy Clin Immunol
2010;126:574-80.e1.
34. Jungersted JM, Scheer H, Mempel M, Baurecht H, Cifuentes L,
Hogh JK, et al. Stratum corneum lipids, skin barrier function
8 Meckfessel and Brandt
and filaggrin mutations in patients with atopic eczema.
Allergy 2010;65:911-8.
35. Jakasa I, Koster ES, Calkoen F, McLean WH, Campbell LE, Bos
JD, et al. Skin barrier function in healthy subjects and patients
with atopic dermatitis in relation to filaggrin loss-of-function
mutations. J Invest Dermatol 2011;131:540-2.
36. 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.
37. 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.
38. 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.
39. Cui CY, Kusuda S, Seguchi T, Takahashi M, Aisu K, Tezuka T.
Decreased level of prosaposin in atopic skin. J Invest Dermatol
1997;109:319-23.
40. Hara J, Higuchi K, Okamoto R, Kawashima M, Imokawa G.
High-expression of sphingomyelin deacylase is an important
determinant of ceramide deficiency leading to barrier disruption
in atopic dermatitis. J Invest Dermatol 2000;115:406-13.
41. Bouwstra JA, Gooris GS, Dubbelaar FE, Weerheim AM,
Ijzerman AP, Ponec M. Role of ceramide 1 in the molecular
organization of the stratum corneum lipids. J Lipid Res 1998;
39:186-96.
42. Castiel-Higounenc I, Ferraris C, Lavalle A, Philippe M, Gaetani Q,
Schmidt R. Exogenous sphinganin derived sphingolipid
increases epidermal ceramide content in human reconstructed
skin. Nouv Dermatol 1999;18:541-6.
43. Simpson E, Dutronc Y. A new body moisturizer increases skin
hydration and improves atopic dermatitis symptoms among
children and adults. J Drugs Dermatol 2011;10:744-9.
J AM ACAD DERMATOL
44. Simpson E, Trookman NS, Rizer RL, Preston N, Colon LE,
Johnson LA, et al. Safety and tolerability of a body wash and
moisturizer when applied to infants and toddlers with a
history of atopic dermatitis: results from an open-label study.
Pediatr Dermatol 2012;29:590-7.
45. Schorr ES, Sidou F, Kerrouche N. Adjunctive use of a facial
moisturizer SPF 30 containing ceramide precursor improves
tolerability of topical tretinoin 0.05%: a randomized,
investigator-blinded, split-face study. J Drugs Dermatol 2012;
11:1104-7.
46. Simpson E, Bohling 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.
47. Huang HC, Chang TM. Ceramide 1 and ceramide 3 act
synergistically on skin hydration and the transepidermal water
loss of sodium lauryl sulfate-irritated skin. Int J Dermatol 2008;
47:812-9.
48. Draelos ZD. The effect of ceramide-containing skin care
products on eczema resolution duration. Cutis 2008;81:
87-91.
49. Wiren K, Nohlgard C, Nyberg F, Holm L, Svensson M,
Johannesson A, 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;23:1267-72.
50. 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.
51. Imokawa G, Yada Y, Higuchi K, Okuda M, Ohashi Y, Kawamata
A. Pseudo-acylceramide with linoleic acid produces selective
recovery of diminished cutaneous barrier function in essential
fatty acid-deficient rats and has an inhibitory effect on
epidermal hyperplasia. J Clin Invest 1994;94:89-96.