Identification and Characterization of Clinical Phenotypes

In this video, Jeff Yu, MD, discusses how clinical phenotypes in AD are characterized and the challenges that come with identification using phenotype data.

Dr Yu is a board-certified dermatologist and fellowship trained pediatric dermatologist practicing at Massachusetts General Hospital in Boston, MA. He specializes in allergic contact dermatitis and occupational dermatitis in adults and children.

Transcript:

How is AD characterized?

Atopic dermatitis is a very heterogeneous type of disease. Clinically, when we see atopic dermatitis, some of the things that we're looking for include, is it red, is it itchy, are there patches in certain areas of the skin that we expect them to be depending on their age? But this can vary, depending on whether you're talking about a neonate, whether you're talking about an infant, whether you're talking about a child, or even an adult.

In very young children, certain locations for atopic dermatitis tends to be mostly on the cheeks, on the trunks, on the outside of the arms, on the front of the leg. So we're talking about the elbow involvement, we're talking about knees. And it tends to be very itchy, so it can be very red, it can be very weepy, it can be very inflamed-looking and sometimes startling to the caregivers. But as kids get a little bit older, the locations tend to move. And these locations then shift to the other side of their arms. So we're talking about the creases of the elbows, back of the knees, back of the neck, places like that.

And in adults, the eczema then can also show up on places such as the hands, especially in people who are working in certain occupations. We tend to see a lot more hand dermatitis in adults, compared to children. And in adults, some of the patches look a lot older. So sometimes the skin might look a lot thicker, it might look a little bit darker in color compared to the ones that we see in children. So we do know that it looks different depending on your age and depending on where you're having it as well.

What strategies exist for determining and subtyping AD phenotypes? How can patients be engaged?

There are various ways of subtyping. So we used to think that atopic dermatitis was like a monolith. We used to think that everybody was similar. You have atopic dermatitis. We know exactly how the disease works. We know that there is a defect in your barrier system. We know that there is a defect in your immune system. However, we know that this is now starting to change a little bit, especially with some of the newer molecular techniques that are available.

And also some of the studies where we're trying to be a little bit more inclusive. We know that the population of United States is changing. We're certainly not just seeing European American patients any more. We are seeing people of various diversity, and some of the strategies of research have focused on what does eczema look like in African-Americans? What does eczema look like in Asian-Americans? What does eczema look like in white Americans? And are they similar or are they different? I think a lot of the older metrics tend to look at more of the white population and less of the skin of color. A bit of the focus has shifted to that.

So in short, in about the last 10 years or so, people have really started to look into how is eczema different and whether or not treatment needs to change and whether or not we need to subtype them. So there are two different ways of subtyping. One way is you can subtype phenotypically, which means that we're subtyping based on the clinical appearance of eczema. So for example, in certain races, eczema can look a little bit different. In people of darker skin color, we may not appreciate the redness that we tend to expect to see in textbook pictures, or we expect to see in these inflamed eczema-like lesions.

In African Americans, for example, we tend to see a lot more lichenification which essentially a word that says the skin is thickened. The skin lines are a little bit more apparent, meaning that they've been itching it for a very long time. In African-Americans as well, the eczema tends to show up more as little bumps, as opposed to these kind of big, scaly patches that we sometimes will see in other populations as well. So that's one way of subtyping it phenotypically.

The other way of subtyping eczema is endotypically, which means that we're really looking at the molecular characteristics. What types of cellular markers are up? What kind of cellular markers are down? In the skin, what type of barrier proteins are missing? And these have really been started to come of age in the last several years with new molecular techniques. And we may be able to focus some treatments based on that alone.

What are some examples of clinical phenotypes of AD?

Locations where the eczema can appear a little bit different. So for example, if we're talking about the hands and the feet where you have eczema involvement, they may not be those big, pink patches that we expect to see. Instead, there are those little bubbles that we see, which are called dyshidrotic eczema. A lot of times those bubbles will appear on the sides of the fingers and places like that, or on the bottom of the feet, as opposed to these larger patches that we expect to see on the trunk, on the flexural folds, in places like that.

And then topographically too, on the face, especially in infants, we tend to see a lot more weepy. We may see more cracking of the skin versus say on the flexural areas like the elbow folds, the back of the knees, places like that. We tend to see a lot more thickening of the skin, accentuated skin lines and such features, depending on the location.

Sometimes age and race can also make a difference, like we had already mentioned. And I think that's also important to take into account too.

Are there any patient-reported data that help inform the clinical phenotype?

There have been a lot of different types of patient studies in recent years asking them to complete surveys, for example. So we're asking patients to say how much does eczema affect your quality of life? So they can kind of check off on a scale. How are you sleeping at night? How does this affect your day-to-day relationships with other people? How does it affect your intimate relationship with your partner? How does it affect your sleep? How does it affect your work life?

All those questions, I think, are extremely important that providers need to pay attention to, because even though someone may have a skin rash that looks relatively mild, and this could be different because of their skin type, could be different because of their clinical phenotype or endotype, the disruption to life could be significant. And that might inform the type of treatment that you give them, where you might be a lot more aggressive with the person who has a lot more significant quality of life influence versus the person that may not and say, "Doesn't really bother me too much." So I think the patient report outcomes are extremely important in management, as well as the diagnosis of atopic dermatitis.

How do you incorporate AD phenotypes into your day-to-day practice, treatment decisions, and coverage processes?

I think that's extremely important. I think having a recognition of all the different types of phenotypes that AD can present as can definitely help you not only just make the diagnosis amongst your patients, but also to make sure that you are doing the right thing for them and picking the right treatments.

So I see a diverse array of patients in my practice. About 50% of them are adults, 50% are children, with a wide range of severity in terms of atopic dermatitis. Patients often come to our referral center because they have rashes that have not been either successfully diagnosed by other clinicians, or successfully treated. So sometimes just by knowing that this person has say, for example, is Middle Eastern or Asian of some sort, and they have a different type of rash, even though it may look like psoriasis, in this case, we do know that sometimes atopic dermatitis in the Asian population can look like psoriasis, but are actually atopic dermatitis. Just by having that in the back of your mind can sometimes help you make the correct diagnosis, and then therefore give them the correct treatment, depending on the type of diagnosis that you're worried about.