Disease Biology and Early Recognition in Atopic Dermatitis

Dr Amy Paller discusses how recognizing pediatric atopic dermatitis as a type 2 inflammatory disease has transformed early treatment strategies, enabling safer and more proactive use of targeted therapies. Learn which clinical and genetic factors—such as early onset, severity, and filaggrin deficiency—predict persistent disease, and how skin barrier dysfunction and immune dysregulation shape the natural history of AD in children.

Transcript

Hi, I'm Dr Amy Paller. I'm professor and chair of dermatology at Northwestern University, Feinberg School of Medicine in Chicago. And I'm an attending and pediatric dermatologist at Lurie Children's Hospital of Chicago.

How has our evolving understanding of pediatric atopic dermatitis as a type 2 inflammatory disease changed the way you approach diagnosis and early intervention in children?

Dr Paller: It really revolutionized our treatment opportunities to fully understand that this is a type 2 inflammatory disease and with the development of agents that in a targeted way can inhibit type 2 immune activation. We really don't have any difference in how we diagnose the disease because at least with everyone I've studied looking at biomarker analysis, every child with atopic dermatitis has a type 2 inflammatory disease. However, I will say that having targeted therapies that really don't require monitoring of labs that have very little in the way of side effects has allowed me to be more aggressive in initiating systemic intervention and feel good about it, feel that I don't have to be worrying about long-term side effects or issues that may come up that affect other systems. So it has moved the needle very much so not only in having new treatment approaches that will allow me to have a better outcome in terms of effectiveness, but also allow me to feel more comfortable in starting more aggressive treatment earlier.

In infants and young children, what clinical or biologic features suggest a higher likelihood of persistent, severe disease rather than transient eczema?

Dr Paller: Well, it's hard to call for everyone, but there certainly are some factors that can increase the persistence of disease. For example, a more severe atopic dermatitis to start with, a young age of onset, having allergy in the family, especially if both parents have allergies, are some of the features. Of course, if you have what's been called ichthyosis vulgaris now with the new terminology, filaggrin-nEDD for non-syndromic epidermal differentiation disorder, if you have that and you have a deficiency of filaggrin, that also tends to lead to more persistent, more severe disease.

What role do skin barrier dysfunction and immune dysregulation play in shaping the natural history of atopic dermatitis during childhood?

Dr Paller: There are many factors that come into play in increasing one's risk of having atopic dermatitis, but the major ones are skin barrier dysfunction and immune skewing towards type 2 inflammatory disease. So these are both important factors in shaping the natural history. As mentioned, individuals who have skin barrier dysfunction, that's a primary issue based on having a genetically triggered reduction in the filaggrin in their skin, resulting in skin barrier dysfunction, have earlier onset, more persistent, more severe atopic dermatitis. This is the primary genetic underlying basis for having atopic dermatitis. Immune dysregulation, of course, is in everyone with atopic dermatitis. There's some evidence that, in addition to type 2, young children with more nummular dermatitis as a component of their atopic dermatitis may have a little bit more Th17 immune dysregulation, perhaps leading to some lesions that are a little more psoriasiform, but that's not been proven in large-scale studies, just several suggesting that.