Abstract
Almost 2 decades ago, Williams and Elias suggested a unifying concept for the pathogenesis
of disorders of cornification, according to which the integrity of the epidermal barrier
and its effective function is an important factor in the regulation of epidermal DNA
synthesis. Interference with the barrier integrity or function will result in epidermal
hyperplasia and may be the primary event leading to hyperproliferative skin diseases,
such as psoriasis.
We have analyzed alterations to several structures of the epidermal barrier that might
be responsible for barrier dysfunction and thus lead to hyperproliferation of the
epidermis in an attempt to repair the barrier and, as a result, might be inducers
of psoriasis. There are several convincing reports indicating that inhibiting of epidermal
transglutaminase may lead to epidermal hyperproliferation and that this stimulus might
trigger psoriasis among genetically predisposed patients.
Disturbance of epidermal barrier function caused by derangement of lipid or cholesterol
or ceramide synthesis leads to increased DNA synthesis and epidermal hyperplasia and
as a result might be an inducer of psoriasis. We could find little evidence to show
that defective defense of the epidermis or an abnormal response of it to bacteria
plays a role in the pathogenesis of psoriasis.
Accumulating data indicate that there is an association of psoriasis and mutations
of genes within the epidermal differentiation complex, which are crucial for the development,
maturation, cornification, cross-linking, and terminal differentiation of the epidermis,
called psoriasis susceptibility locus 4.
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