Optimizing Treatment of Pediatric Atopic Dermatitis - Episode 13
Amy Paller, MD: The pathophysiology of atopic dermatitis is increasingly well understood, and it has really gone a long way in directing new therapies for the disease. It has basically shown us that it's quite complex. We have the barrier abnormalities, which may be primary or secondary to the immune abnormalities, which show a very strong skewing, particularly toward Th2 [T helper cell type 2] immunity with some Th22, IL-22 [interleukin-22] increases, as well.
We have found that there is also a component, of course, from the environment, including from microbiome changes in terms of altering the abnormal immune responses, as well as the barrier defect in itself. It's really not one thing or another, because everything is interrelated.
Certainly, we see some differences in the appearance of atopic dermatitis, especially in young children, versus in adolescents and adults. And we've done a fair amount of work looking at some of the molecular differences at varying ages. We initially showed that infants have some differences, particularly in their increase in some Th17 skewing, and their near lack of any increases in the Th1 pathway that are seen in the adults. We see a gradual shift toward the adult molecular fingerprint as children get older, and then become adolescents and then adults.
But I would say that across the board we're still talking about this same predominant skewing toward Th2 immunity and that increase as well in IL-22 that we think may be involved in some of the lichenification and hyperproliferation of skin. I think we're on the right pathway with many of the agents that we're using. We still see in children increases in interleukin-31, for example, which we know is that itch cytokine that's so important, as well.
We don't see early on, quite the same barrier abnormalities in terms of expression of protein with reductions in filaggrin and some of those other proteins and differentiations. But we certainly do see some of the lipid barrier abnormalities. We see the abnormalities in transepidermal water loss. We do see that very quickly on that develops now, and we start to see, possibly because of greater chronicity with the immune changes, the reductions in the barrier proteins, even in the young children.
Transcript Edited for Clarity