Delving Into Clinical, Epidemiological Differences of Adult, Pediatric Atopic Dermatitis

Despite atopic dermatitis (AD) being commonly considered a pediatric disease, Jonathan Silverberg, associate professor of dermatology, director of clinical research and patch testing, George Washington University School of Medicine and Health Sciences, opened his discussion Friday at the 2022 American Academy of Dermatology (AAD) Annual Meeting by highlighting the high number of adults with AD, whose disease has different clinical features than seen in younger patients.

Silverberg, during the session, “Atopic Dermatitis in Adults: Not Just Big Kids,” said that data on AD may show a smaller percentage of adults have the disease compared with children. However, from a population standpoint, there are markedly more US patients with adult AD than there are with pediatric disease.

Moreover, as patients age, the risk of more severe AD grows as well. An estimated 5.9 million US adults have moderate to severe disease.

“The problem is we know very little about [adolescent and adult] subsets of patients clinically," he said. "So there's a lot of gaps there in terms of our knowledge.”

In looking at the genetics of AD, several genetic mutations have been considered as major risk factors for AD development, particularly interleukin receptors and filaggrin (FLG). However, in looking at the significance of these mutations across age groups, research has shown that FLG presents more prominently in patients who developed the condition in infancy or early childhood, noted Silverberg, whereas FLG mutations were not associated with AD that began in adolescence or adulthood.

“When we think about these pathways, there's some provocative work from multiple labs around the world that have suggested that maybe the relative proportions of different pathways being activated is different between children and adults," Silverberg said.

“It also makes you wonder, if you say that there's different pathways that are upregulated, does that change the potential forecast, prognosis, or theranosis of using targeted therapies? We actually haven't seen it yet, but it's certainly something that we're trying to be avant garde about—can there be a precision medicine approach, where we can then look at either morphology or other biomarkers, and be able to predict response.”

The influence of FLG was also indicated to be exclusive to populations of European descent; even in high-risk areas like the United Kingdom, only 20% to 50% of patients present with this mutation.

“The truth is, we know almost nothing about the genetic underpinnings and the differences across different racial and ethnic subgroups. And probably the group we know the least about is in Latin America, and for Hispanic patients around the world,” he added.

Delving into the age-related clinical manifestations of AD, the core features of the disease were indicated to be similar overall, but differences have been observed between children and adults that may be due to pathophysiologic differences.

Specifically, Silverberg said that adults are more likely than children to present with more signs of chronic disease, hand eczema, and a stronger relationship of disease activity with emotional factors. Comorbidity risk was also referenced, in which adult patients are more likely to have increased risk of cardiometabolic, mental health, allergic, bone, and infectious conditions.

Emotional effects of the disease, such as stress, are seen as a common trigger of disease flares among adult patients with AD. To cope with the disease, patients were more likley to avoid intimate relationships, going outdoors during different times of the year, bathing, exercise, swimming, and certain foods.

With 36.1% of adult patients with AD reporting at least 3 itch triggers, Silverberg cautioned that although recognizing these factors can provide nontherapeutic strategies to manage disease, abstaining from certain tasks or hobbies can have a notable impact on quality of life. These strategies also cannot replace the effectiveness of pharmacologics, he added.

“I think we have to recognize that when we talk about trigger avoidance, I actually don't agree with the idea that it should be the cornerstone that every patient must have all the trigger avoidance before going to therapy. It's part of the shared decision-making," Silverberg said.

“We really need to be careful about empiric food avoidance diets, particularly in pediatric patients…at least if patients are going to avoid certain foods, clinically at least make sure they're seeing a nutritionist, someone who can guide them to make sure that they have a well-balanced diet because if they do this without guidance, they will get themselves into trouble from time to time.”

Several new topical, oral, and injectable drugs have come to market to treat AD, and he said disease severity should be considered when deciding the optimal treatment choice and dosage.

For clinicians using a step-up approach, Silverberg said dosing and dose titration of biologics and Janus kinase (JAK) inhibitors would be different across disease subsets:

• mild AD: no use for either oral JAK inhibitors or biologics
• frequent moderate AD flares: low-dose JAK inhibitor use or biologic use
• seasonally severe AD: no use for biologics, high-dose JAK inhibitor use followed by down-titration
• moderate AD with severe episodes: biologic use recommended or phases of low-, high-dose intervals of JAK inhibitors
• chronic severe AD: biologic use or high dosage JAK inhibitor use recommended
  

“These [subsets] are all different. They all have different treatment considerations, and if you're trying to come up with a one size fits all treatment approach, you're not going to be doing your patients any favors," he said.

“Any of the patients with chronic disease would benefit from a biologic, because you need long-term control and there are drugs that are certainly safe enough and effective enough to be used long-term, but you should not be using it for that seasonally severe/intermittent patient. I think that intermittent patients are a subset that have been missed, as there just wasn’t anything to offer them. Now, I think the JAK inhibitors opened up the ability to treat a whole new segment of the population that has been left untreated today.”