From basket weave to barrier. Unifying concepts for the pathogenesis of the disorders of cornification

Consequences of beta-glucocerebrosidase deficiency in epidermis. Ultrastructure and permeability barrier alterations in Gaucher disease.

“…Establishment of a competent epidermal permeability barrier, therefore, requires conversion of glucosylceramides to ceramides. Epidermal lipids, in addition to their established role as mediators of the permeability barrier, also influence desquamation (46). For example, inborn errors of lipid metabolism appear to play a role in the pathogenesis ofcutaneous lesions in recessive X-linked ichthyosis (47), Refsum disease (48), Sjcgren-Larsson syndrome (49), and neutral lipid storage disease (50).…”

Thematic review series: Skin Lipids. Pathogenesis of permeability barrier abnormalities in the ichthyoses: inherited disorders of lipid metabolism

“…In neonates who survive the perinatal period, the plate-like encasement is shed, and the phenotype shifts to a severe ichthyosiform erythroderma (9,190). Transcutaneous water loss rates remain extremely high (47), explaining at least in part the prominent epidermal hyperplasia and hyperkeratosis that are presumably driven by the permeability barrier abnormality, as described above.…”

“…All of the ichthyoses studied to date, whether primary disorders of lipid or protein metabolism, have demonstrated a permeability barrier abnormality (9,10,13). Because permeability barrier requirements generally drive metabolic responses in the underlying epidermis (15,16), the clinical phenotypes in the ichthyoses almost certainly reflect a best effort attempt by the epidermis to normalize barrier function (9).…”

“…Because permeability barrier requirements generally drive metabolic responses in the underlying epidermis (15,16), the clinical phenotypes in the ichthyoses almost certainly reflect a best effort attempt by the epidermis to normalize barrier function (9). These metabolic responses to a flawed barrier, although only partially successful, usually suffice to allow survival in a dry, terrestrial environment.…”

Revised nomenclature and classification of inherited ichthyoses: Results of the First Ichthyosis Consensus Conference in Sorèze 2009

“…8 Differences in the pathogenetic mechanisms of these disorders have to be considered, but from a functional viewpoint, the ichthyosis skin phenotype may be regarded as a summation of the genetic epidermal barrier defect and the homeostatic response. 8,172 This concept is illustrated by a recent mouse model, where Alox12b (e/e) skin was transplanted on nude mice. The neonatal Alox12b (e/e) mouse phenotype presented with thin, highly inflamed skin leading to dehydration and death within several hours (genetically impaired SC barrier), but the transplanted rescued adult phenotype of the lipoxygenase-deficient skin developed a mouse ichthyosis with severe hyperkeratosis (homeostatic response).…”