Identifying and Classifying Atopic Dermatitis in Children and Adults

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EP: 1.Identifying and Classifying Atopic Dermatitis in Children and Adults

EP: 2.Targeting the clinical, economic and payer considerations of atopic dermatitis

EP: 3.Clinical Burden of Atopic Dermatitis and Comorbidities

EP: 4.Direct and Indirect Costs of Atopic Dermatitis

EP: 5.Cost-Benefit Analyses in Atopic Dermatitis

EP: 6.Oral and Topical Therapies for Atopic Dermatitis

EP: 7.Building Out Treatment Formularies for Atopic Dermatitis

EP: 8.JAK Inhibitors for Atopic Dermatitis

EP: 9.JAK Inhibitor Treatment Selection for Atopic Dermatitis

EP: 10.Unmet Needs in the Treatment of Atopic Dermatitis

EP: 11.Barriers to Treatment Access in Atopic Dermatitis

EP: 12.Increasing Access to Effective Therapies for Atopic Dermatitis

Peter A. Lio, MD: Atopic dermatitis is a very interesting disease because there are multiple components to its pathophysiology. At its core, there are two big pieces of this puzzle. The first is skin-barrier damage. We know that the skin barrier is not working optimally, and I like to call this leaky skin because that means water gets out and allergens, irritants, pollutants, and even pathogens can get in. On the other side of this story, we have inflammation. The immune system, possibly in part because of the reaction from these allergens and irritants in the skin, abnormally is going crazy, driving inflammation and itch. These two feedback into each other, creating this vicious cycle that brings in other aspects of the pathophysiology, including the microbiome, which is in disarray, including changes in the nerve endings and even behavioral changes. We know that this can affect the entire person from every aspect that we can think of.

Our knowledge of atopic dermatitis has undergone incredible and rapid transformation in the past decade. When I started getting interested in this disease, it was a backwater of medicine and dermatology. We didn’t have a lot of specialized knowledge of any of the players of this entire cascade of pathophysiology. Now we’re inundated with all these new concepts, so we understand that it’s a vicious cycle. We understand better some of the key players in terms of the immune system, inflammatory mediators like interleukin IL-4, IL-13, and IL-31, the master itch cytokine, and many others. Finally, we’re starting to put the puzzle pieces together. I often think about this. I call this the virtuous cycle of drug development. For a long time, we didn’t have specialized or specific drugs for atopic dermatology. We used things like topical corticosteroids and other anti-inflammatory agents, but we didn’t have anything that could target the specific mediators. Now we’re starting to see these come out and be developed, and what’s neat is that as we get specific mediator blockers or modulators, we learn more about the disease.It has been an incredible time of growth and change. I’m pretty sure this is just the beginning. This is the tip of the spear because we have over 100 medications in development. The next 10 years are going to be a roller coaster of excitement, so get ready.

Atopic dermatitis is a fairly heterogeneous disease. There are different presentations depending on the patient’s background and age and sometimes just the day of the week. We have some patients who have multiple presentations on their skin even at the same time. The classical vision of this disease and the classical descriptions are that there is an eczematous eruption. We often use the term “eczema” synonymously with “atopic dermatitis.” They’re not technically synonymous, but the eruption is described as eczematous: it’s red and scaly, and there’s often some induration where it’s swollen or puffy. But it can go all the way from very acute changes, where it’s scratched open—so it can be open, oozing, and eroded—to the more chronic changes, where it becomes thick and leathery. We use the term “lichenification.” All of these are in the spectrum.

There are even other aspects. There’s a perigal pattern, where you get these very distinctive, itchy bumps. We have Lichen simplex chronicus, where there are targeted areas that get thick and leathery skin with enhanced skin markings. And there are follicular patterns, where all the little hair follicles can look like goosebumps or like keratosis pilaris, but it can be a form of eczema.

It’s interesting to see all these presentations and that make it challenging, particularly when we take in different skin types.More richly pigmented skin has certain patterns that are more common there, and it’s also more difficult to see redness when there’s more pigment in the background of the skin. There can be some confusion about the severity too. With very light skin you can say, “OK, it looks really red,” but that can also be misleading the other way. Medium tones are in the middle, and darker tones can be hard to appreciate redness, so there’s a lot of complexity around this disease. On top of all that, we don’t have a gold standard test. Unfortunately, there’s not a simple blood test or even a skin biopsy that can tell us for sure that this is atopic dermatitis, and sometimes that makes our job very tough.

Severity is a tricky question because there are some validated scales that work very well, but there are well-known limitations. One of the limitations we’ll see most commonly in clinical trials is called the IGA, the Investigator Global Assessment. Recently it’s been validated again, and we have what they call the VIGA-AD, the Validated Investigator Global Assessment for Atopic Dermatitis. That’s a great one. It is a five-point scale—0, 1, 2, 3, and 4—where 0 is clear, 1 is almost clear, 2 is mild, 3 is moderate, and 4 is severe. It’s very easy to do, and clinicians can do that as well. I put that on every eczema patient I see. I give them an IGA score because you’re saying it already: You’re going to say it’s mild, moderate, or severe. It’s 2, 3, or 4—easy peasy. The problem is there are a lot of limitations with this.

First, because it’s so digital with only five options. One can imagine there’s an infinite variety of severity in the real world, and you could miss things like severe. What about more severe? Well, it’s still severe. What about crazy severe? Well, it’s still severe. What if that crazy-severe patient gets a little better? They could still be severe. You miss things because it’s so crude. On the other hand, it’s also a point estimate: How do they look right there at that moment? Patients sometimes come in and say, “I know I look bad today. I’ve been good, but I went by my cousin’s house yesterday, and I’m all flared up.” Or they’ll say the opposite: “I know I look good today.” Maybe they’re almost clear that day. You’re thinking we’re doing great, and they say, “No, the last three months have been terrible. I just happened to be a little better,” because this is a waxing-and-waning disease.

There are a number of tools that can be applied, but they have limitations. What we’re seeing more is a patient-oriented approach. We’re looking at outcomes and how the patient is describing their quality of life and some of those indices. Sleep is another one that I ask about because sleep is so important and obviously not just sleep the night before. I want to know in the last couple of weeks or the last month, how has sleep been? These are the end points we’re looking at more to get a better sense of what the disease is doing.

For children and adults, there can be some differences. In babies in particular, they often develop more on the face and neck, and the cheeks are very commonly involved. Sometimes we’ll talk about this headlight sign. The cheeks are bright red, maybe the rest of the face is also red, but the nose is usually spared so it looks like a little headlight of lighter skin in the sea of red. As we get into the more toddler and general pediatric ages, we’ll see the classical flexural patterns: the antecubital fossa and the popliteal fossa. We’ll see more localized disease for some patients that can be more severe than others, of course. In adults, it tends to become more acral, so hands and feet tend to be involved more. There’s also a variant called the head and neck dermatitis variant, where we’ll see almost a seborrheic dermatitis variation that’s red and scaly, and it can be unpleasant for our young adults.

Transcript edited for clarity.