title: Stratum corneum structure and function correlates with phenotype in psoriasis.
abstract: Psoriatic epidermis demonstrates a defective program of growth and differentiation, including an abnormal permeability barrier. Despite the fact that damage to the epidermis often initiates the disease, psoriasis is commonly viewed as triggered by aberrant immune phenomena in deeper skin layers. Permeability barrier homeostasis requires the formation and secretion of lamellar body contents, as well as the extracellular processing of lamellar body contents into lamellar bilayers. To address the hypothesis that psoriasis is triggered by exogenous rather than internal factors, we assessed permeability barrier function, lamellar body structure, and extracellular lamellar bilayer formation in untreated patients with different psoriatic phenotypes. Subjects with erythroderma and active plaque phenotypes displayed elevated transepidermal water loss levels, increased numbers of epidermal lamellar bodies (many of which failed to be secreted); i.e., corneocytes displayed retained cytosolic lamellar bodies, and extracellular domains largely devoid of lamellae. In contrast, patients with chronic plaque psoriasis and sebopsoriasis displayed a lesser increase in transepidermal water loss, normal numbers of lamellar bodies with only a few retained organelles, and abundant extracellular lamellar material (although a normal unit bilayer pattern did not form). Thus, both functionally and structurally, permeability barrier homeostasis was more disrupted in erythrodermic and active plaque psoriasis than in chronic plaque psoriasis and sebopsoriasis; i.e., the extent of defective barrier function correlated with abnormalities in the known mechanisms of barrier repair, including lamellar body production and extracellular bilayer formation. These findings are consistent with the hypothesis that both the initial appearance of psoriasis (Koebner phenomenon) and changes in disease phenotype are driven by alterations in barrier function.
authors.affiliation: Dermatology Service, Veterans Administration Medical Center, San Francisco, CA 94121, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ghadially
authors.forename: J T
authors.initials: JT
authors.lastname: Reed
authors.forename: P M
authors.initials: PM
authors.lastname: Elias
mesh_terms: D002908:Chronic Disease; D003873:Dermatitis, Exfoliative / Q000473:pathology; D004817:Epidermis / Q000473:pathology; D006801:Humans; D008566:Membranes / Q000473:pathology; D008854:Microscopy, Electron; D010641:Phenotype; D011565:Psoriasis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D012867:Skin / Q000473:pathology* / Q000503:physiopathology*