Dr Elaine Siegfried on Considerations for Systemic Therapy Use in Pediatric Atopic Dermatitis

Among the subset of pediatric patients with atopic dermatitis who have moderate to severe disease, use of systemic therapies is typically considered for children who cannot achieve skin clearance with certain amounts of topical corticosteroids or who present with exacerbating atopic comorbidities, said Elaine Siegfried, MD, professor of pediatrics and dermatology, Saint Louis University Health Sciences Center.

Transcript

Can you discuss considerations for the use of systemic therapies among pediatric patients with atopic dermatitis?

First-line therapy for mild to moderate atopic dermatitis is always topical. And the mainstay of treatment is skin care with bland emollients and frequent bathing—we use bleach baths. But beyond that, there are some children whose skin can't stay clear on a safe amount of topical corticosteroids, so we use corticosteroid-sparing topical agents. The most frequently used are calcineurin inhibitors—pimecrolimus and tacrolimus. Then after that, we have another FDA-approved treatment, a PDE4 [phosphodiesterase 4] inhibitor, crisaborole. And then there are others in the works. A new one was just approved, a topical JAK [Janus kinase] inhibitor ruxolitinib, but that's topical therapy.

There are a subset of patients, probably in the 10% to 20% range of children who have AD, that have more moderate to severe disease, and those kids we use systemic treatment for. So, how do you decide who's beyond topical treatment? There are a whole variety of factors.

The first one, and the most simple one, is probably for children who can't stay clear using corticosteroids in a safe amount. So that is no more than what I say in my practice is 15 days a month and then depending on the potency of the topical corticosteroid, how many grams a month we have to use. That particular parameter is not well accepted or worked out. Even though topical corticosteroids have been around for 50 years, we just do not have great handle on the frequency and the quantity for safe use of topical corticosteroids.

But there are many children, especially children whose body surface area is over 15% or 20%, it's really hard to use topical treatment to manage the disease at all; it's very difficult to understand. So, adherence tends to be very poor; people can't understand how much to use. And then some kids just can't tolerate topical treatment because they have a relative hyperesthesia. So, they have a burning and stinging sensation that prevents their use. These are children who typically aren't sleeping, which means their parents aren't sleeping, so they have a lack of good tolerance for topical treatment and topical treatment just becomes impossible.

The other real big barrier to topical treatment is access. In our complicated system of different types of insurances, it's just really hard, because different insurances have different formularies and they often limit topical quantities of medication. For example, for a child that we want to give corticosteroid-sparing to, and we give them pimecrolimus, especially if they're under age 2, we can't get enough medicine for them.

Most insurances will only give us 100 grams a month, despite the fact that in clinical trials we're using 100 grams a week for these children. So, access to medication, including topical medication, is hard and that's a complicating factor for children who need more aggressive topical treatment.

Then there are lab parameters that we can check for children who are beyond topical treatment. Sometimes children have lab abnormalities, like a really high total IgE [immunoglobulin E]. Not everyone with AD has that, so it's not a great biomarker, but the higher your total IgE level, the more likely it is that you're not going to be able to be treated with systemic treatment.

And then other atopic morbidities. So, children who have allergic rhinitis, who have asthma along with their atopic dermatitis are good candidates for systemic treatment. But even the choice of systemic treatment is complicated and difficult to navigate, especially with regards to medication access.

Finally, I actually wanted to mention that a subset of children who have atopic dermatitis also are prone to infections. Their skin barrier is compromised so they have relative, what we call, cutaneous energy. We know that they're very susceptible to Staphylococcus aureus colonization. Frankly, all of them are colonized with Staphylococcus aureus, but some subset of children are more susceptible to other kinds of infection—frequent strep skin infections, strep throat, otitis media.

And then there's children who have frequent and recurrent herpes, often in an occult fashion. You can't really tell by looking at them that they have herpes, but they have widespread herpes, we call that eczema herpeticum. They can also get widespread coxsackie, a condition we call eczema coxsackium, [and] widespread molluscum. Unlike kids with normal skin barrier who might have 5 to 10 lesions, these kids will have hundreds of lesions. And unlike children with a normal skin barrier where the molluscum can persist for about a year, these children can have molluscum persistently for 5 years or longer.

So, these are all children that we take into consideration for needing systemic therapy.