Table 2.

Key Points

1	A variety of unrelated mutations that compromise epidermal barrier function predispose to the development of atopic dermatitis (AD).
2	An acquired deficiency in filaggrin also occurs, independent of mutation status.
3	These mutations converge on the lamellar body secretory system, producing abnormalities in either lamellar body formation, secretion, or post-secretory processing that compromises extracellular lamellar bilayer structure
4	Theses secretory abnormalities account in large part for the distinctive lipid abnormalities in AD, which included a global decrease in barrier lipids; a further decline in ceramide content; and truncation of the chain lengths of free and esterified fatty acids.
5	The same pathogenic sequence compromising antimicrobial defense accounts at least in part for colonization by S. aureus and other pathogens in AD.
6	Based upon the above, rational therapy should address and correct filaggrin status, and/or the lipid abnormalities in AD.