Paola Facheris, PhD: Distinctions in Adult-Onset and Pediatric Atopic Dermatitis

Paola Facheris, PhD

New late-breaking data presented this month at the European Academy of Dermatology and Venerology (EADV) 2022 Meeting showed distinct inflammatory characteristics in adult-onset atopic dermatitis relative to standard, child-onset atopic dermatitis.

The data, presented by Paola Facheris, PhD, a post-doctoral fellow at the Laboratory of Inflammatory Skin Diseases at Icahn School of Medicine at Mount Sinai, contributes to an evolving understanding of how increasing rates of adult-onset atopic disease is activating—and how clinicians may potentially tailor treatment for it.

In an interview with HCPLive during EADV 2022, Facheris discussed her lab’s research into atopic dermatitis pathology, these latest findings, and the implication of recent clinical drug development as it relates to the growing disparity between child-onset and adult-onset atopic dermatitis.

HCPLive: First and foremost, could you help us define our known history and interpretation of TH1 and TH2 activation in atopic dermatitis?

Facheris: In our lab, we wanted to first explore the different phenotypes and endotypes of atopic dermatitis. Our lab is well known for this kind of research. Before talking about TH2 and TH1 pathways, I would like first to define what kind of disease we're talking about. We're talking about atopic dermatitis, but in this case, we are considering atopic dermatitis in the adult populations. So classically, atopic dermatitis is known to be a childhood disease. However, about 7% of the adult population suffers from atopic dermatitis. But, we can make a distinction between the age of onset of atopic dermatitis in the adults.

So, it was thought until 20 years ago that most of the forms of atopic dermatitis that we see in the adult patients are the ones that start in childhood, and they are persistent or remitting in the adult age. But about 20 years ago, for the first time we used the term "adult-onset atopic dermatitis," meaning that there are patients with atopic dermatitis that have symptoms for the first time after 20 years of age. So after that, for about 20 years, there has been a lot of reports about this kind of atopic dermatitis, and what it looks is this subtype is different from the one that's started at childhood, in terms of risk factors and clinical appearance. There are typical forms, where we have involvement of the head and neck area, the hands and feet, and we have atypical forms, in terms of clinical appearance.

So our lab started from the questions, "Is this form of atopic dermatitis similar to the one that started in childhood or is it different? What is the molecular profile of these 2 diseases?" So we started from these questions, and we analyzed the transcriptomic profile in skin of these patients and we analyzed the proteomic expressions in serum of the patients. So, atopic dermatitis is known to be a TH2 and TH22 disease, meaning that we have a hyper activation of all the cytokines and interleukins related to this pathway—like IL-4, IL-5, and IL-13.

And what we found out is that both diseases share these common upregulations. They both have a strong TH2 and TH22 upregulations. However, the magnitude of these changes is higher in the form since childhood, and we have a modulation of the other immune pathways. So the form of atopic dermatitis that we call pediatric-onset atopic dermatitis is not only TH2 and TH22, but it's also TH17. And on the opposite side, the form of atopic dermatitis with adult onset is more of a TH1 component that we don't see in the pediatric one. And this TH1 component is present in lesional skin, in no lesional skin, and also in the serum of these patients. And we have a very nice correlation between the TH1 markers in serum and skin of these patients, meaning that this pathway is contributing to this disease and is something atypical of this form of atopic dermatitis.

Our interpretation and valuation into these inflammatory pathways as they're impacting patients with atopic disease, such as adults with atopic dermatitis, is hugely implicated given the state of available, emerging and investigative biologics in the space right now. Is this something that there's any potential agents within consideration or for proposal that could address this pathway more directly?

Facheris: I mean, we are in a lucky period for atopic dermatitis. There are a lot of agents that are in the pipeline, about to be released on the market or under investigation. So this is a good moment for atopic dermatitis. I would say dupilumab—we know it's the first biologic that was approved for atopic dermatitis, and is targeting mainly the TH2 pathway. So in this case, dupilumab is indicated for older dose form with TH2 upregulations. But, in case of adult-onset atopic dermatitis, ideally, you would want a drug that is able to target also the TH1 pathway. So, something that has a more broad effect—like for example, JAK inhibitors could be good drug, or those drivers that are able to impact the T cells regardless of the pathway they belong to, for example, OX40, it's a good target for these patients or CCR4 can also be another good target.

Speaking of dupilumab, they had a very significant indication achieved within treating atopic dermatitis earlier this year: the youngest eligible pediatric population, aged 6 months to 5 years, received FDA approval in the US. Obviously, with these findings, it would probably elucidate the question of whether we would see greater benefit nonetheless for our adult-onset atopic dermatitis patients.

Would these findings begin to better influence guidance, even guidelines and recommendations, for treatment and care strategies within atopic dermatitis as these drugs become available across all the age populations?

Facheris: Yeah, exactly. That's exactly the point. We will have a lot of drugs on the market, and being able to characterize the disease, being able to choose the right molecule for the right patients will be the goal. Dupilumab, exactly like what you were saying, is a great drug. It's safe, it is suitable for all ages. That's what we have learned. However, when it comes to difficult populations, like adult-onset atopic dermatitis it's possible that dupilumab won't be able to cover this TH1 activation. So that's the main reason why we need to stratify the patients and we need to find the right target for each of them.

As we understand it, pediatric allergic and atopic disease is increasing annually. It really warrants the need for such expansion of availability—obviously, better diagnostics, better interpretation of biomarkers and observable risks. We stay focused so much on the inherent and developed risk at early stages for atopic disease.

Is it something that we're also seeing increasing in adults as well? Is adult-onset atopic dermatitis on the rise?

Facheris: It is exactly like you are saying. We see an increase not only in the pediatric population, but also in the adult population. In the United States 26% of all the adult patients that suffer from atopic dermatitis report an adult onset of the disease. But in other countries like Italy, up to 60% of patients report this kind onset of symptoms after 20 years of age. So it's something that we need to pay attention to. We need to ask the patient, to investigate their story, to see if they have any had any risk factors or any personal history of atopic dermatitis. But apparently, this is something that is emerging and increasing. I think dermatology should be more aware of this form of atopic dermatitis.