Both psoriasis and atopic dermatitis are considered multigenic disorders, meaning an inherited predisposition to develop one of these is carried on more than one gene. In addition to bad genetic luck, usually some environmental (or non-genetic) factor(s) is necessary to trigger the disease. In recent years, studies of populations have determined that variations (‘polymorphisms’) in genes that are involved in the skin barrier as well as genes of the immune system are linked to the development of both of these common skin disorders. Now it appears that these two vulnerable systems – the barrier and the immune systems – interact in the pathogenesis of both disorders, but with notable differences.
For example, a few years ago studies from Japan by Hatano and coworkers demonstrated that the T cell abnormality (i.e., inflammation produced by Th2 cells) in atopic dermatitis contributes to the barrier abnormality by suppressing synthesis of ceramides, one of the key lipids required for formation of a competent skin barrier. Psoriasis, however, displays a different type of immune response, dominated by Th1 cells that generate a different profile of signaling molecules or ‘cytokines’. And psoriasis usually displays a much less severe barrier abnormality that atopic dermatitis.
Cytokines of Th1 cells have been previously shown to increase antimicrobial defense in skin. This stands in contrast to the cytokines of the Th2 cells in atopic dermatitis, which down-regulate antimicrobial defense. These differences in interaction between the immune system and the antimicrobial barrier of skin probably account for the clinical observation that patients with psoriasis are not typically plagued by skin infections, while infections are a much more common and vexing clinical problem for those with atopic dermatitis.
Now, new research by Sawada and colleagues shows that the Th1 cytokines in psoriasis also increase ceramide levels. This observation could account for the lesser barrier abnormality in psoriasis.
Bottom line: Both atopic dermatitis and psoriasis are likely due in part to inherited defects in the skin’s permeability barrier. But genetic differences in the inflammatory responses to their inherited barrier defects – differences that either amplify or mute the barrier defects – can begin to account for some of the distinct clinical features of these two common skin disorders.