The Pathophysiology of Atopic Dermatitis

Transcript:

Lawrence Eichenfield, MD: Hello, and welcome to this HCPLive® Peer Exchange titled “Advances in the Management of Atopic Dermatitis.” I’m Dr Lawrence Eichenfield. I’m a professor of dermatology and pediatrics at the University of California San Diego and the chief of pediatric and adolescent dermatology at Rady Children’s Hospital–San Diego. I’m very happy to have great cofaculty today. Joining me in this discussion is Dr Raj Chovatiya.

Raj Chovatiya, MD, PhD: Hey there. I’m an assistant professor of dermatology at Northwestern University Feinberg School of Medicine in Chicago, Illinois. It’s great to be here.

Lawrence Eichenfield, MD: Dr Leon Kircik.

Leon Kircik, MD: Hi, Larry. Hello everyone. Thank you for inviting me. My name is Leon Kircik. I’m a clinical professor of dermatology at Icahn School of Medicine at Mount Sinai in New York City. I also have my clinical practice, as well as a research center in Louisville, Kentucky.

Lawrence Eichenfield, MD: Dr Peter Lio.

Peter Lio, MD: Hello, and thank you for having me. I’m Peter Lio. I’m a clinical assistant professor of dermatology and pediatrics at Northwestern University Feinberg School of Medicine in Chicago, Illinois. I’m also the founding director of the Chicago Integrative Eczema Center.

Lawrence Eichenfield, MD: And Dr Elizabeth Swanson. Hi, Lisa.

Elizabeth Swanson, MD: Hi, everybody. Thank you so much for having me. I’m Lisa Swanson. I’m a dermatologist and a pediatric dermatologist in Boise, Idaho, and I work in private practice at Ada West Dermatology as well as St. Luke’s Children Hospital.

Lawrence Eichenfield, MD: Thank you for being here. Our discussion will focus on standard of care for the management of atopic dermatitis, such a common condition, while providing insights into the newer mechanisms of action being studied, specifically JAK inhibitors that are in the drug-approval pipeline. Welcome, everyone. Let’s get started.

We’re going to start with an overview of atopic dermatitis and some of the burden of the disease. Let’s start off looking at the pathophysiology. What’s our modern sense of the pathophysiology of atopic dermatitis? How has our knowledge evolved over time? Raj, can you get us started?

Raj Chovatiya, MD, PhD: Sure. It’s important to think about the pathophysiology of atopic dermatitis, because that helps us understand the reasons why there’s so much heterogeneity in the disease itself and why treatments differ from patient to patient. I like to think of atopic dermatitis as being an interplay between a couple aspects, the epidermal barrier dysfunction and immune dysregulation. All this is happening in a background of differences in environmental and genetic factors. That’s why people talk about atopic dermatitis having outside-in and inside-out mechanisms. In terms of the skin barrier, studies have shown that there’s lower expression of certain proteins related to epidermal differentiation. Filaggrin is 1 of those that people have studied a lot. There are differences in tight junctions, the things that prevent water from leaking out of your skin, and differences in concentration of lipids and ceramides, which is basically the glue that holds the skin together.

Oftentimes, when you have differences in leakiness and permeability in this barrier, you react to different external insults: microbes, allergens, toxins, and irritants. This altogether causes immune cell activation. In particular, we think about this concept of type 2 immune skewing with atopic dermatitis. What does that mean? Basically, Th2 cells guide this program with a bunch of cytokines that you’re probably somewhat familiar with, IL-4 and IL-13, and this perpetuates a lot of the inflammation that we see in atopic dermatitis. And then this feeds forward into furthering the epidermal barrier dysfunction as well. Additionally, there are other inflammatory mediators produced by a variety of cells in the skin, but this captures how there are a lot of things going on, both on inside and outside the skin.

Lawrence Eichenfield, MD: That was a great overview, Raj. It’s interesting how we spend a lot of time talking about inherent barrier dysfunction and emphasize that. Then there’s immune mediation disease, and we know it all cycles together.

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Transcript edited for clarity.