Emma Guttman, MD, PhD, reviews the complex pathophysiology of atopic dermatitis and the differences between adults and children.
Peter A. Lio, MD: We’ve learned so much about atopic dermatitis, but I’m fascinated to hear from Emma: what have you learned recently? You’ve been directly involved in some of the understanding about the pathophysiology of atopic dermatitis. How has our knowledge evolved over time?
Emma Guttman, MD, PhD: That’s a great question. Our greater understanding of pathophysiology led to more treatment because for a long time, there was confusion. We had futile discussions about whether to use an inside-out or outside-in approach. We now understand that, while the barrier is important in atopic dermatitis, what perpetuates the disease course and brings it from nonlesional stage to acute disease, and even more to chronic disease, are the immune abnormalities. We are talking about the elevation of immune cytokines, particularly those that belong to type 2, such as IL-4, IL-13, IL-31, IL-5, as well as IL-22, which derives from type 22a T cells. These are increased in acute disease and even more in a chronic stage disease.
The important thing is that the type 2 axis, the immune axis, and the cytokines such as IL-4 and IL-13, are shared among all the atopic dermatitis phenotypes. There are several disease phenotypes. You mentioned them in children and adults, and there are other phenotypes based on ethnicity and age. Atopic dermatitis seems to be a bit of a heterogeneous disease, but the common immune axis that is upregulated in all these phenotypes is the type 2 immune axis.
There are some differences. For example, children will have more Th17 [T helper 17 cells] involvement than adults. The type 2 immune axis is shared in all of them, and we now see it through targeting the Th2 axis in both children and adults, with different agents being successful and meaningful for our patients. That’s my 2 cents.
Peter A. Lio, MD: The outside-in/inside-out approach, you suggested that it’s not a useful designation, but may it contain some knowledge about some of the endotypic or phenotypic differences? Or should it just be thrown away, and we’re going to have new and better ways to understand?
Emma Guttman, MD, PhD: When we talk about the different phenotypes that have differences in some immune pathways, they may also have some differences in barrier relevant factors, and I’ll give you an example.
For example, African American patients, when compared to European Americans, have a high H2 upregulation similar to European Americans. But unlike the European Americans who also have involvement of the Th1 axis, that immune axis is missing in African Americans. They also, for example, unlike the European Americans who have abnormalities in filaggrin, African Americans are lacking these abnormalities, in large part. They have only a 3% filaggrin mutation, whereas in European Americans, we are talking about 12% to 30% in Europe. Besides that, they also don’t have inhibition of filaggrin when you look at their skin.
There certainly are differences, but there are also some commonalities. Among the commonalities are the fact that all of the patients have immune abnormalities, particularly type 2 abnormalities, and all of them have barrier abnormalities, though they may be different barrier abnormalities. Lipids are also abnormal in African Americans, and claudin is abnormal in African Americans, but there are some differences among the phenotypes.