JAK inhibitors for the Management of Atopic Dermatitis (AD) - Episode 1
Eric Simpson, MD, MCR; and Alexandra K. Golant, MD, provide an overview of the pathophysiology of atopic dermatitis and detail how to approach an atopic dermatitis diagnosis.
Linda Stein Gold, MD: Hello, and welcome to this HCPLive® Peer Exchange titled JAK Inhibitors for the Management of Atopic Dermatitis. I'm Dr Linda Stein Gold, the director of rheumatology clinical research at Henry Ford Health Center in Detroit, Michigan. Today, I'm thrilled to be joined by my colleagues and friends Dr Raj Chovatiya, who is the assistant professor of dermatology at Northwestern University Feinberg School of Medicine in Chicago, Illinois; and Dr Eric Simpson, a professor of dermatology at the Oregon Health and Sciences University in Portland, Oregon; and Dr Alexandra Golant, the medical director at the dermatology faculty practice and the program director of the dermatology residency program at Mount Sinai in New York City. Let's go ahead and get started.
It is such an exciting time in atopic dermatitis and our understanding of the disease has evolved quite a bit. We now have a lot more targeted therapies.
Eric, let's start with you. Could you give us a little bit of an overview on our understanding of the pathophysiology of atopic dermatitis?
Eric Simpson, MD, MCR: Thanks so much, Linda. I agree. It's been an exciting time. I'm happy to be here to share some exciting news. When I think about the pathophysiology of atopic dermatitis, it's a large topic. It's difficult to think about, and there are a lot of advances recently, as you noted, but I still go back to 2 main factors that are involved: barrier dysfunction and immune hyperresponsiveness. I use terms like that—maybe not quite so technical with my patients—like saying that you have a dry skin barrier problem and that your immune system is too hyperactive. We've been arguing for years about what's more important—the skin barrier or inflammation. I don't think it's been answered yet, but those are the 2 big factors I think about. There are influences on those 2 factors: genetic and environmental. I also talk to my patients about how this is really a genetic disease. Between 70% and 85% concordance of atopic dermatitis is found in identical twins. Once patients recognize that, I almost say that you've been programmed from birth to get this, and it alleviates some of the guilt involved in thinking that they're causing this condition themselves. That's how I frame it for my patients and how I think about it in my mind. The last part is understanding this inflammatory hyperresponsiveness. When you look at the latest studies, type 2 inflammation is extremely important, and we know that from bedside to bench understanding. When we have all of these trials, it seems like the ones that are working for all phenotypes is type 2 blockades. The treatment tells us about the disease, but there's more than just type 2. As we know from a lot of the basic science work, there are components of type 1 inflammation or components of type 17 or TH17 and IL17 in certain subgroups. It's a little broader than just type 2, but type 2 is important.
Linda Stein Gold, MD: Do you feel like there's a difference in the disease between different ethnicities? Is this all 1 disease or do you think it's different?
Eric Simpson, MD, MCR: Right. My colleagues will chime in on this one, but from the responses to the AD-directed therapies, it's more a singular disease with variation in phenotype and in manifestations than it is different individual diseases, and that's my bias. It's hard to confirm necessarily, but the broad responsiveness to directed therapies makes me feel like they're more similar than they're different despite the clinical heterogeneity.
Linda Stein Gold, MD: I would agree with you. Ally, let's get practical. When a patient comes into your office, how do you clinically assess them? How do you make sure you're making the correct diagnosis? What are your thoughts?
Alexandra Golant, MD: That's a great question. Atopic dermatitis differs from some of our other inflammatory skin diseases that we see and treat because the disease has 2 main components that you see clinically. They're equally important to assess in any given patient, and that is the skin disease or the clinical eczema or eczematous lesions, and then the pruritus that these patients suffer from. Clinical assessment of the disease, or diagnosis or even categorization of disease severity, has to take into account these 2 main components to get a global sense of how the disease is impacting their life, which directly correlates to how aggressively we choose to treat this disease in these individuals.
Linda Stein Gold, MD: Do you notice any particular challenges in making the diagnosis, or is it usually clinically obvious when a patient comes in?
Alexandra Golant, MD: The textbook cases of atopic dermatitis are clinically obvious, but not all patients read the textbook. For patients that come in with a childhood-onset disease with a strong personal or family history and a textbook itch-and-skin disease, the diagnosis is very apparent. But, increasingly, we're recognizing, as Eric alluded to, that just due to the clinical heterogeneity of this disease, more atypical presentations occur, for example, in adult-onset disease in patients that do not have a personal family history of atopic disease or any strong history that they recall. If you look at the criteria set out by the American Academy of Dermatology, the absolute essential criteria to make this diagnosis is not that difficult. We don't have to find that much, at least based on the 2014 guidelines; it's eczematous skin lesions, it's the pruritus, or the itch, and it's either a chronic or relapsing course. When you just get down to the basics, that is not a difficult diagnosis to make, but it is sometimes difficult for someone to let go of these supportive criteria like the childhood-onset or the atopic history.
Linda Stein Gold, MD: Yeah. We're starting to understand that this disease can occur at other ages. It's not necessarily just in those children under the age of 5.
Transcript Edited for Clarity