Atopic Dermatitis Overview: Pathophysiology, Diagnosis, and Burden

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EP: 1.Atopic Dermatitis Overview: Pathophysiology, Diagnosis, and Burden

EP: 2.Treatment for Mild to Moderate vs Moderate to Severe Atopic Dermatitis

EP: 3.JAK Inhibitors in Atopic Dermatitis: Historical Use and Mechanisms of Action

EP: 4.Topical Ruxolitinib Use in Atopic Dermatitis

EP: 5.Recent Approval of Oral JAK Inhibitors for Atopic Dermatitis

EP: 6.Atopic Dermatitis: Practical Advice on Selecting and Using JAK Inhibitors

EP: 7.Ongoing Challenges in the Management of Atopic Dermatitis

EP: 8.Key Takeaways on the Management of Atopic Dermatitis

Transcript:

Christopher G. Bunick, MD, PhD: Welcome to this DermatologyTimes® Viewpoints presentation titled, “Innovations in the Treatment of Atopic Dermatitis.” I’m Dr Christopher Bunick, a physician-scientist and associate professor of Dermatology at Yale University School of Medicine in New Haven, Connecticut.Today, I’m joined by 3 of my colleagues: Dr Jeffrey Cohen, assistant professor of Dermatology at the Yale University School of Medicine in New Haven, Connecticut; Dr Linda Stein Gold, director of Dermatology Clinical Research at the Henry Ford Health System in Detroit, Michigan; and Dr Peter Lio, clinical assistant professor of Dermatology and Pediatrics at Northwestern University’s Feinberg School of Medicine and partner at Medical Dermatology Associates of Chicago. Welcome to all of you.

Our discussion today is about the current state of care in atopic dermatitis, with a focus on the role of several recently approved Janus kinase, or JAK, inhibitors in the treatment spectrum. Welcome to our audience as well, and let’s begin.

Our first segment is going to be an overview of atopic dermatitis and some of the conventional therapies. Dr Stein Gold, I will begin with you. How has our knowledge regarding the pathophysiology of atopic dermatitis evolved over time?

Linda F. Stein Gold, MD: Well, it certainly has evolved, and it’s constantly changing and we’re learning more and more. We understand that there’s really several components that go into the pathogenesis of the disease. We know there’s a genetic component, we know there’s barrier dysfunction, and we also know there’s an abnormality of the immune system. So, when we think about the genetic component, the filaggrin abnormality is probably the best studied of the genetic abnormalities, and we see this filaggrin abnormality across different ethnicities. We also know if you have a family history of the disease, you’re more likely to have it, especially if 2 of your parents have atopic dermatitis.

When we look at the barrier, we know it doesn’t work quite as well as it should. It tends to be leaky, so it has a hard time keeping the outside world out and the inside world in, and we see an increase in transepidermal water loss and we see an influx of potential antigens, and this can trigger the immune process. Then, when we look at the immune dysregulation, we understand that this primarily involves a type-2 immune response, and we see an upregulation of these certain proinflammatory cytokines including IL [interleukin]-4, IL-13, IL-31, TSLP [thymic stromal lymphopoietin], IL-22, interferon gamma. With our knowledge of what’s going on in the immune system, we are now able to better target some of our treatments to really hone in on the abnormalities and the pathogenesis.

Christopher G. Bunick, MD, PhD: That’s a wonderful response, and filaggrin is certainly near and dear to my heart as my research lab looks into filaggrin. Dr Cohen, how do you clinically assess and diagnose atopic dermatitis, and do you see any differences in patients of different age groups and demographics?

Jeffrey Cohen, MD: Yes, that’s an important question because before we can effectively treat atopic dermatitis, we need to make the correct diagnosis. In many cases, this is a clinical diagnosis, and we’re looking for generally pink thin plaques or patches that come in the flexural areas—in the elbows, antecubital fossae, behind the knees, popliteal fossae. These tend to be itchy, and we often see signs that patients are scratching on top of that. Sometimes atopic dermatitis can be confined to these areas, but in other times it can be much more widespread, impacting almost any area of the body.

There are other things that tend to help us consider whether a patient has atopic dermatitis. One of them is the symptoms that they experience. Itch is a very prominent feature of atopic dermatitis and almost every patient we see with atopic dermatitis is itchy. It’s also important to note that in various skin types, it can look different. In lighter skin tones, we see pink, we see red. However, in darker skin tones, it may look more hyperpigmented or even violaceous. Sometimes it can be confusing to make the diagnosis because it can look different in different skin tones, but as dermatologists, it’s important that we be able to make a good diagnosis of a common condition, atopic dermatitis, in any sort of patient.

In difficult cases, there can also be other things that help point towards atopic dermatitis, things like hyperlinear palms, seeing more lines in the palms of the hand, hyperpigmentation, darkness around the eyes, Dennie-Morgan lines, which are prominent lines beneath the eyes. Things like this in challenging or unclear cases can also help point you in the right direction.

Christopher G. Bunick, MD, PhD: Great. Dr Lio, building off these first 2 wonderful answers, can you please discuss how common atopic dermatitis is and what is its clinical burden for our patients, and what about the impact on quality of life? We hear about quality of life nowadays with patients. How does it affect them and their families?

Peter A. Lio, MD: Yes, I think there is a tremendous burden of disease, and it’s not only on the patient, right? It’s on their entire support network—the family, the friends, school, work. It keeps rippling outwards, and I would even argue that it even affects clinicians, people taking care of patients with bad atopic dermatitis feel some of that burden as well. It is staggering, frankly. Now, we know that there are some direct burdens from the disease itself. The appearance of it is, of course, very disheartening for many patients, and the itch is mind-bogglingly bad for some patients. There have been some studies that show patients are feeling itch for more than 12 hours of every single day. So essentially every waking moment they’re feeling itch.

There’s the impact on sleep, and, of course, when somebody’s sleep is impacted, that, of course, has a whole bunch of ramifications further down the line. They’re not able to focus, concentrate. We know there’s also very real physiologic changes that happen from poor sleep or sleep deprivation, including, unfortunately, damaging the skin barrier. So we get stuck in these vicious cycles of disease that keep propagating it.

That’s sort of a sense of the burden, and I think it’s very difficult to quantify that burden because there are some things we can measure, like absenteeism, you miss work, you miss school, great, but it’s harder to measure something like presenteeism. You’ve made it, you got up, you dragged yourself out of bed, there’s blood on your sheets, you’re totally exhausted. You’re half not there, your mind is elsewhere, you’re distracted, you’re feeling itchy, but we count you as present at school that day, so it’s tricky to see that.

Now, this might not be so bad if this were just a few people sprinkled about the population, but we know that the prevalence of atopic dermatitis is very high. That incidence keeps going up and up and up, and some of the most current numbers suggest that on the order of 10% and some even as high as 20% of children, particularly in the United States, but we know there’s some variation around the world and in different parts of the world, depending on the amount of urbanization, the exposure to pollutants, things like that, can affect this number. But maybe for adults, somewhere between 3% and as high as 10% of adults are affected as well. So there really are quite a lot of people who are affected by this disease, and I think again the costs of that are really compounding, in an aggregate are really staggering.

Christopher G. Bunick, MD, PhD: That’s wonderful, Dr Lio. I think the numbers end up being over 100 million Americans alone have some form of atopic dermatitis. It’s tremendous. I really liked what you talked about quality of sleep. One of the things that my patients complain about is they can’t just even go into a swimming pool because of the itch, the pain that happens. So just children wanting to swim with their friends. It’s amazing how just the simple things of life are so affected by atopic dermatitis.

Transcript edited for clarity.