Transcript
Dr. Christopher Bunick (00:07):
I'm Dr. Christopher Bunick, Associate Professor of Dermatology at the Yale School of Medicine.
(00:12):
When we think about atopic dermatitis pathophysiology, there are six major cytokines that drive that. Traditionally it's IL-4 and IL-13, but also we know about IL-31, TSLP, IL-22, and interferon-gamma. During the more acute phases of atopic dermatitis, we think that IL-4, IL-13, TSLP, L-31 play an important role, and this is reflected in some of the histopathology that we see in atopic dermatitis where we see a lot of spongiosis or kind of that fluid-filled epidermis and dermis, where that wetness that we see in a lot of skin lesions of atopic dermatitis is reflected histopathologically.
(00:55):
But in more chronic lesions, that's not always the case. In more chronic atopic dermatitis, we often see lichenified thickened plaques on the skin. This is largely driven by different cytokines than in the acute phase of atopic dermatitis. In particular, we think of interleukin-22 and interferon-gamma playing a role in the more chronic stages of atopic dermatitis. With interleukin-22, one of the things that we know is that it plays a major role not only in lichenification thickening of the skin in chronic AD, but it's pretty commonly upregulated in head and neck atopic dermatitis, which has proven to be a little bit more difficult area to treat.
(01:37):
With interferon-gamma, one of the effects of upregulated or increased levels of interferon-gamma as it downregulates ceramide synthase. When you have lower ceramide synthase, you have impaired lipid content in the skin, and this also is an important consequence in chronic atopic dermatitis that contributes to that dry thickened skin that some patients see.
(02:01):
Lastly, I'd like to point out that in your more chronic atopic dermatitis lesions, we also know that fibroblasts play an important role in driving some of the fibrosis-like changes, and fibroblasts, are very sensitive to a number of cytokines, including interleukin-13, which can drive some of this fibrosis. That also can be seen in the histopathological analysis of atopic dermatitis.
