The evolution of the pathophysiology of atopic dermatitis, including clinical presentation of disease and the differences between children and adults, is examined.
Lawrence F. Eichenfield, MD: Peter, when it comes to the pathophysiology of atopic dermatitis, how has our knowledge evolved?
Peter A. Lio, MD: It’s remarkable. In some ways, we have come a tremendous distance. In other ways, we haven’t moved very far at all. The complex part about this condition is that it is not easy. We have those early diseases that were 1 gene mutation, 1 pathophysiological pathway. They were simple to solve. This 1 is multifactorial, multipronged, and really complex because it has a number of vicious cycles or positive feedback loops.
We know that these have been understood for a long time, particularly the itch-scratch cycle. We know that there’s a huge inflammatory component to this disease. We’ve also known that the skin barrier is damaged. That has been true since at least the 1950s. There was probably some sense even earlier on that these aspects were playing a role.
We are at a point where we’ve begun to fill in all the blanks. We’re starting to understand and name those mediators, which importantly allows us to pick therapeutic targets. Just a couple of years ago, we had our first biologic agent, which allowed us to pick a very specific inflammatory mediator and block that. Fortunately, the proof was in the pudding. It seems to work, so now we are finally at the tip of this spear of all these new therapies coming.
That’s how we learn about a disease. We have a hypothesis about how it works, but you don’t really know until you can actually show that you can control it. Finally, we were able to do that. What’s fascinating to me is that no matter where you start on this spectrum, whether you have impaired skin barriers—for example, a filaggrin gene mutation at birth—or if you have an inflammatory problem at the first point, we know that they all get involved.
This concept that the entire sphere of all these pieces of the puzzles are involved no matter where it begins—this domino effect—is really important. It has also shaped our thinking about how to get people better. We need to do multipronged approaches for therapy as well to keep things at bay. Because if you just stop inflammation, that doesn’t help the skin barrier. It doesn’t help the dysbiosis of the microbiome. It doesn’t help the behavioral and neural piece. We’re continuing to learn about these details.
Lawrence F. Eichenfield, MD: That was great.
Elizabeth A. Swanson, MD: I’d be so interested to hear more about what you think about the whole idea of dysbiosis. We now know that the normal flora of people with atopic dermatitis is often different from the normal flora of people who don’t have atopic dermatitis. I don’t think we know which comes first, the chicken or the egg. Is the dysbiosis a result of the inflammation in barrier issues, or are the barrier issues and inflammation occurring because of the dysbiosis? What are your thoughts and feelings about how that fits in?
Peter A. Lio, MD: It was fascinating for me to watch that translation too. When I learned it years ago, we were taught that Staphylococcus aureus was a colonizer; an opportunistic infection that could happen sometimes. It wasn’t doing anything. Since Dr Heidi Kong’s great work with the National Institutes of Health a few years ago in particular, we’ve begun to switch this around. Now there is a very powerful and compelling narrative that Staph aureus is a primary driver of disease, at least in some patients.
We now understand that it’s releasing a number of toxins like delta toxin, which has an immune-instigating effect, and alpha toxin, which damages keratinocytes directly. We’re beginning to understand that dysbiosis is a primary driver in at least some patients. If we can control that and get the bacteria back to normal, we might be able to help cool things down. Larry, do you agree that that’s changed?
Lawrence F. Eichenfield, MD: Yes, to a degree. Although, the intercalation of staph was really well known. Dr Heidi Kong’s work updated the technology where we had just done cultures as compared with genomic evaluation.
I do want to comment about what Peter was saying. I’d probably change some of the wording because you said the anti-inflammation doesn’t change the barrier or the microbiome. It does change it, but it may not change the fundamental fact that they’re changed in atopic dermatitis compared with not having atopic dermatitis. Those are some of the cool data coming out. If you do a systemic, biologic agent, for instance, it improves staph, decreases colonization, and decreases staph infections clinically on the skin. And that controlling inflammation improves barrier function. There is this cycle between barrier dysfunction/inflammation, inflammation/barrier dysfunction, and the microbiome tied together.
There are a few intriguing studies that are in process where people are trying to use the microbial approach to see if they can control inflammatory eczema by putting certain sets of microbes on the skin. That will be really interesting to see.
Peter, what’s your sense of acute, subacute, and chronic forms or the difference in presentation between kids and adults?
Peter A. Lio, MD: It’s confusing because sometimes you’ll see all 3 forms in a given patient at the same time. Of course, different patients at different times can show different forms and subtypes. In general, very acute disease is often open, oozy, really eroded, and there’s often a staph component.
The subacute is more edematous, puffy, swollen, and sometimes looking somewhat like urticarial patches and plaques. in the more chronic forms, we’re thinking about more lichenification or prurigo nodularis-type patterns. I feel like it’s often mixed and can change pretty dynamically over time.
One of the hardest things for me is that many patients bring photos to us. We have people bringing photo albums, sometimes dozens and dozens of photos. We don’t necessarily need to see that many. Because it’s such a dynamic disease, people will say, “I was been fine until a couple of days ago, and now it’s terrible,” or the opposite, “I can’t believe that every time I come and see you I’m doing pretty good, but let me show you how I looked last Wednesday.” There is this dynamic aspect, which makes it harder to quantify the disease sometimes.
Lawrence F. Eichenfield, MD: Yes. There’s no hemoglobin A1C for eczema.
Jeffrey M. Bienstock, MD, FAAP: Not yet.
Lawrence F. Eichenfield, MD: Do you think that the pathophysiology is different between kids and adults?
Peter A. Lio, MD: So far, I’ve treated them very much the same way. Obviously, we’ll tailor our treatments for a smaller patient, a younger patient, or someone with more sensitive skin, but I largely approach them the same and with a similar overall strategy. We’re learning with some of the biomarkers in terms of both epidermal barrier changes and inflammatory changes that they are probably different.
One day, we may be able to say, “There are important differences between pediatric and adult atopic dermatitis.” One question is whether it’s just an issue of the chronicity. Are we more likely to see that pattern in adults because of change over time, or are they really 2 distinct nosological entities? I’m excited to find out which is true and how that can affect our approach to understanding and treating the disease.
Lawrence F. Eichenfield, MD: That’s a great comment and well summarized. In clinical practice, we don’t have those differences yet. The immunologic differences that have been found in some clinical studies haven’t translated to our different approach to a 5-year-old, a 10-year-old, or a 35-year-old. It may in the future as we tease out the aspects of the whole training of the immune system. We’re going to be studying very much how early mediation of disease may impact the course over time. It will be intriguing.
Transcript Edited for Clarity