The impaired skin barrier function in atopic dermatitis

is also caused by a reduced lipid content or

impaired lipid composition in the epidermis atopic
dermatitis. In particular, a decreased content for the
total amount and for certain types of ceramides has
been described.80 A decrease in covalently bound
ceramides91 and a reduced sphingomyelinase activity
have been found in atopic dermatitis. Also, decreased
lamellar body secretion, which is predominantly composed
of lipids, with subsequent entombment of lamellar
bodies within corneocytes, has been reported.92TION AND
PSORIASIS: EPIDERMAL
HYPERPROLIFERATION AND
THE SKIN BARRIERKIN BARRIER
(See also Chapter 18)
Psoriasis is a chronic, generalized, and scaly erythematous
dermatosis that is primarily localized in the
epidermis, showing highly enhanced proliferation and
disturbed differentiation, which leads to hyperkeratosis
and parakeratosis. In addition, there is a neutrophilic
infiltrate in the beginning and in particular in
severe cases of psoriasis; later on a moderate Tlymphocytic
infiltrate is present. Because of this
severely disturbed proliferation and epidermal differentiation,
there is an impaired barrier function.93 The
level of TEWL is directly related with the clinical severity
of the lesion: high TEWL in acute exanthematous
psoriasis; a moderate increase in TEWL in the chronic
plaque type of the disease. Abnormalities in the SC
intercellular lipids, especially a significant reduction in
ceramide 1, have been found.94 Electron microscopy
studies disclosed severe structural alteration of the
intercellular lipid lamellae.95 A genetic linkage of psoriasis
to the epidermal differentiation complex 1q21
has been found. Within the epidermal differentiation
complex, the SPRRs are highly upregulated in psoriasis
plaques.96 Also, the association of psoriasis with
cytokeratin K17 has been discussed.
ICHTHYOSIS: THE PATHOLOGICAL
ICHTHYOSIS: THE PATHOLOGICAL
LACK OF MOISTURE IN THE EPIDERMIS OF MOISTURE IN THE EPIDERMIS
(See Chapter 49)
Ichthyosis comprises a group of monogenetic diseases
expressing a disturbed desquamation resulting
in scales and a mild-to-moderate barrier defect. They
are caused either by changes in epidermal lipids or by
changes in epidermal differentiation. XLRI is a noncongenital
ichthyosis, consisting of a generalized desquamation
of large, adherent, and dark brown scales.
The metabolic basis of XLRI is an enzymatic lysosomal
deficiency of steroid sulfatase or arylsulphatase C.
Complete deletions of the STS gene mapped to the
Xp22.3-pter region have been found in up to 90% of
patients. The reduced cholesterol sulfatase activity
leads to accumulation of cholesterol sulfate and a
reduction of cholesterol and consequent abnormality
in the structural organization of the intercorneocyte
lipid lamellae.97–99
Ichthyosis vulgaris is the most common monogenetic
skin disease. Recently, loss-of-function mutations in the
gene encoding filaggrin that cause ichthyosis vulgaris
have been described. During terminal differentiation,
profilaggrin is cleaved into multiple filaggrin peptides
that aggregate keratin filaments. The resultant matrix is
cross-linked to form a major component of the cornified
cell envelope. Reduction of this major structural protein
leads to an impaired keratinization and to a moderate
defect in skin barrier function.100
Transglutaminase 1 is responsible for the cross-linking
of several cornified envelope proteins. Therefore,
deficiency in transglutaminases 157 leads to lamellar
ichthyosis which is a more severe disease than ichthyosis
vulgaris with a defect in filaggrin only.
TREATMENT IMPLICATIONS AND
APPROACHES: RESTORING THE
SKIN’S PROTECTIVE FUNCTION
Treatment strategies in inflammatory diseases often
address immunogenic abnormalities and barrier
function. Treatments with cyclosporine, tacrolimus,
pimecrolimus, and UV light have been shown to
reduce cell inflammation as well as to improve barrier
function, thus helping to normalize proliferation and
differentiation. Topical steroids, although clinically
effective, do not lead to the repair of the disturbed skin
barrier function seen in AD.101 However, because of
their side effects, all of these treatments should be used
for a short time only. In contrast, application of bland
creams and ointments containing lipids and lipid-like
substances, hydrocarbons, fatty acids, cholesterol
esters, and triglycerides can be used without side
effects for long-term treatment of mild-to-moderate
inflammatory diseases. Creams and ointments partially
correct or stimulate barrier repair and increase
SC hydration,44,102–104 thus influencing epidermal proliferation
and differentiation.15 It has been proposed
that a lipid mixture containing the three key lipid
groups [(1) ceramides, (2) cholesterol, and (3) free fatty
acids] is able to improve skin barrier function and SC
hydration in AD.105 Also, the efficacy of ceramide 3 in a
nanoparticle cream in atopic dermatitis has been
described.106 However, because several research
groups and companies report that creams containing
ceramides and a mixture of the three key lipids are not
superior to “classical” cream or ointment preparations,
such preparations have not yet been widely used.
KEY REFERENCES
KEY REFERENCE
8. Bouwstra JA, Pilgrim K, Ponec M: Structure of the skin
barrier. In: Skin Barrier, edited by PM Elias, KR Feingold.
New York, Taylor and Francis, 2006, p. 65
10. Elias PM: Epidermal lipids, barrier function, and desquamation.
J Invest Dermatol 80:44s, 1983
25. Roop D: Defects in the barrier. Science 267:474, 1995

30. Candi E, Schmidt R, Melino G: The cornified envelope:

A model of cell death in the skin. Nat Rev Mol Cell Biol
6(4):328, 2005
44. Jensen JM, Proksch E, Elias PM: The stratum corneum of
the epidermis in atopic dermatitis. In: Skin Barrier, edited
by PM Elias, KR Feingold. New York, Taylor and Francis,
2006, p. 569
49. Brandner JM, Proksch E: Epidermal barrier function:
Role of tight junctions. In: Skin Barrier, edited by PM
Elias, KR Feingold. New York, Taylor and Francis, 2006,
p. 191
81. Proksch E, Foelster-Holst R, Jensen JM: Skin barrier function,
epidermal proliferation and differentiation in eczema.
J Dermatol Sci 43(3):159-169, 2006
86. Irvine AD, McLean WH: Breaking the(un)sound barrier:
Filaggrin is a major gene for atopic dermatitis. J Invest Dermatol
126:1200, 2006