Advances in pediatric eczema treatment

Dr. Sugarman provides his insight on the most significant changes in pediatric eczema treatment over the last few years. (Ольга_Тернавская - stock.adobe.com)

It’s an exciting time in pediatric eczema research. Scientists are doing controlled studies to answer patients’ and families’ basic and commonly asked skincare questions. On the other end of the eczema research spectrum, investigators are studying novel molecules that target specific immune abnormalities, which are changing the lives of many children and teens who suffer with moderate-to-severe eczema, according to Society for Pediatric Dermatology President Jeffrey Sugarman, M.D., Ph.D.

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Dr. Sugarman, a clinical professor of dermatology and family medicine at University of California San Francisco and in practice at Redwood Family Dermatology in Santa Rosa, Calif., shares what he says are big changes in the last few years in what we know about pediatric eczema, or atopic dermatitis.

SETTLING A LONG-HELD DEBATE
Dermatologists have long debated if a bad skin barrier or abnormal immune response causes atopic dermatitis. Researchers are finding that it’s probably both, according to Dr. Sugarman.

“There’s evidence on both sides. It’s an important question because it directs our therapeutic management and the way we research how to best manage atopic dermatitis,” he says.

SKINCARE RECOMMENDATIONS
Basic aspects of eczema skincare, like best bathing practices, haven’t been well studied. But that’s changing, he says.

In one study, researchers compared frequent soaking baths, twice daily for two weeks, followed by the application of an occlusive moisturizer (the soak and seal method) to infrequent bathing, twice weekly for two weeks, for atopic dermatitis management. Subjects in the randomized clinical trial with a single blind cross-over controlled design used the same moisturizer, cleanser and class 6 topical corticosteroid.

“The only thing that varied was the bathing,” Dr. Sugarman says. “What they found was that the twice daily soak and seal baths improved eczema severity more than restricting baths to twice a week. Now we have something that we can tell patients and their families with a little bit of data to back it up.”

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Another basic question has been whether it is better to apply topicals to damp or dry skin. Researchers conducted a randomized, controlled trial comparing topical steroid application to wet versus dry skin in children with eczema.
“It turned out that it didn’t make a difference whether you applied the topical corticosteroid to presoaked damp skin or dry skin in terms of the effectiveness,” Dr. Sugarman says.

Bleach baths can play an important role in Staphylococcus aureus infection and colonization, according to Dr. Sugarman. Amy Paller, M.D., and colleagues studied the impact of treating Staphylococcus aureus infection and colonization with either nasal mupirocin and dilute bleach baths or just petrolatum and dilute bleach baths. The paper published in 2009 in Pediatrics suggests that nasal mupirocin plus bleach baths more effectively managed S. aureus infection in those with atopic dermatitis compared to petrolatum and bleach baths.

“Pretty much everybody with atopic dermatitis is colonized with Staph, and in some patients, the Staph overgrows and causes clinical signs of infection,” Dr. Sugarman says. “A lot of the idea behind using bleach baths is could we reduce colonization with Staph aureus to try and control the disease because Staph can be a trigger in flaring up atopic dermatitis. It’s turning out to be more complicated. Some now think it’s actually the anti-inflammatory effects of dilute bleach rather than the antimicrobial effects that would account for some of the improvement in atopic dermatitis we see in those who use bleach baths once or twice a week.”

Jonathan Silverberg, M.D., and Ph.D., and colleagues conducted a metanalysis on to help determine whether bleach baths effectively treat atopic dermatitis. Their results published in 2017 suggest using bleach baths were not more effective than just a plain water bath.

“There are some caveats here. It’s a metanalysis and some of these trials were done in different ways. But sometimes it’s useful to look at a collection of studies to try to guide us,” Dr. Sugarman says.

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Researchers also are studying whether other bathing additives, like vinegar, or acetic acid, make a difference for atopic skin. Researchers divided patients into several groups. There was a plain water bathing group. There was a water plus bleach at a dilute concentration. And then there was water plus dilute vinegar or acetic acid for treatment of atopic dermatitis,” he says. “We don’t have data on yet, but it’s a study that’s ongoing and we will have data probably in the next six to 12 months.

BIOMARKERS WILL BE BIG NEWS
Biomarker research is hot – not just in atopic dermatitis but also in other areas in dermatology, according to Dr. Sugarman.

“Specifically related to atopic dermatitis, the idea is that the immune system worsens the skin barrier in atopic dermatitis and that blood levels of the activated molecules in atopic dermatitis can serve as a surrogate to skin immune activation. That may correlate with disease severity,” Dr. Sugarman says. “Dr. Paller’s group has undertaken a very ambitious study to look and see if there are actual biomarkers that we can measure to predict who is going to have severe atopic dermatitis and how we can monitor improvement and worsening of disease at the micro level. This data isn’t out yet but in the next couple of years this is going to be an explosion of really interesting biomarker data.”

GAME-CHANGER TREATMENTS FOR KIDS WITH ECZEMA
“Let’s talk about the immune system,” Dr. Sugarman says. “We know there is an abnormal immune response in those affected by atopic dermatitis, and the most exciting data we’ve had in a long time for management of atopic dermatitis is the astonishing results for Dupixent (dupilumab, Sanofi and Regeneron) for those with moderate-to-severe atopic dermatitis.”

Dupilumab is an inhibitor of key cytokines interleukin (IL)-4 and IL-13. The FDA has approved dupilumab in adolescents as young as 12 for treating moderate-to-severe atopic dermatitis that has failed standard therapy, according to Dr. Sugarman.

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“We were one of the investigative sites for the pivotal adolescent trial. I have to tell you that my personal experience with this drug is remarkable. I’ve seen patients with severe recalcitrant disease who failed topical and systemic therapies, that have responded really well to Dupixent,” he says.

Researchers are currently studying dupilumab for atopic dermatitis in the 6- to 11-year-old age group.
“I would suspect that if this data that looks like the adolescent data that Dupixent is going to be approved down to age 6,” he says.

There’s another molecule called lebrikizumab (Dermira), which is similar but inhibits only IL-13.
“Dermira just completed phase 2 trials, and I was the medical monitor for those trials. Those phase 3 trials are going to start very soon. The trials are in adults, which is the standard paradigm. You start in adults and move down to adolescents and younger children. But I would expect this to be a big buzz once they complete their phase 3 trials,” he says.

JAK ATTACKS
Another class of molecules called Janus kinase inhibitors (JAK) inhibitors are taking aim at atopic dermatitis. Researchers are studying oral ruxolitinib (Jakafi, Incyte), in atopic dermatitis patients with mild, moderate and severe disease.
“In order to be in this trial, you have to have a body surface area of between 8% and 20% affected skin. These are pediatric subjects age 2 years to 17 years,” Dr. Sugarman says.

There are other JAK inhibitors in clinical trials for atopic dermatitis: the oral agent upadacitinib (Rinvoq, Abbvie) and a cream formulation delgocitinib (Leo Pharma), baricitinib (Eli Lilly) and the JAK 1 inhibitor PF-04965842 (Pfizer) is in phase 3 trials in adolescents.

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“JAK molecules regulate inflammatory processes in the skin, so by inhibiting the JAK pathway you can work on this abnormal immune response,” Dr. Sugarman says.

MORE ON THE PDE-4 FRONT
The FDA approved phosphodiesterase-4 (PDE-4) inhibitor crisaborole (Eucrisa, Pfizer) for children as young as 2 years.
“There are new topical PDE-4 inhibitors being evaluated as well. One is MM36 (Medimetriks). They are in the middle of clinical trials so I would expect more information about those molecules in the next year or two,” Dr. Sugarman says.
There’s no one treatment that’s going to work for everybody, according to Dr. Sugarman.

“Treatment needs to be individualized based on age, severity of disease and the location of skin that’s affected by atopic dermatitis,” he says. “We really need as many tools in the toolbox as possible.”

References:

Dr. Sugarman is a consultant and speaker for Regeneron, Sanofi and Pfizer.