Treating a Child With Severe AD: From Topicals to Biologics

Doug Brunk

March 03, 2022

When children with atopic dermatitis (AD) present to the clinic and their parents complain that no previously recommended medical therapies have worked, what's the next step?

"Many patients who have failed topical steroids have never had adequate treatment," Anna Yasmine Kirkorian, MD, chief of dermatology at National Children's Hospital in Washington, said during the ODAC Dermatology, Aesthetic & Surgical Conference. "There is no lower age limit on the use of topical corticosteroids, and low potency corticosteroids are inadequate to treat severe eczema. The idea that only over-the-counter 2.5% hydrocortisone cream is necessary is not true," she added.

"You also want to scrutinize the vehicle," she said, noting that children are often prescribed cream formulations that hurt when applied, so parents stop applying them. "Ointments are generally the vehicles of choice in childhood," she added.

It is generally not advised to use topical and oral antibiotics in children with AD, unless there are clear signs of infection. "If they're just slightly oozy, don't use them," she continued. "Of course, every child or adult with eczema has Staph aureus on them, but most of the time, what you need to do is repair the barrier. We know that from data and common sense. When we repair their barrier, their rates of infection decrease."

A focal area with pustules and pus should be cultured and treated, Kirkorian said. "Monotherapy with antibiotics is going to do nothing for you." In cases of children with failure to thrive, she recommends referral to pediatric dermatology, allergy/immunology, GI, or genetics, as appropriate.

For children with severe AD, Kirkorian favors a rescue plan with a one-pound jar of triamcinolone ointment 0.1%. She recommends application of the ointment to all areas, including the face and scalp once nightly for 2 weeks, with a follow-up appointment at the end of that time. "If you just give people medicine and ask them to come back in 6 months, they are not able to comply with that and they don't have faith that it's going to work," explained Kirkorian, associate professor of dermatology and pediatrics at George Washington University, Washington. At the end of 2 weeks, "the majority will have improved dramatically, and then you can implement maintenance therapy with topical calcineurin inhibitors, crisaborole, or possibly topical ruxolitinib."

Some clinicians prescribe oral antihistamines for AD, but Kirkorian said that data supporting their use are limited and antihistamines are not approved for use in children younger than 6 months of age. Sedating antihistamines will induce sleep, "but do not provide durable night-long sleep," and routine use may have an impact on learning and school performance. In addition, exposure to antihistamines in children under age 2 may be associated with development of ADHD at school age.

The interleukin-4 receptor alpha antagonist dupilumab (Dupixent) is approved by the Food and Drug Administration for moderate to severe AD in patients ages 6 and older. But obtaining it for patients can be tricky, she said, as this requires documented failure of corticosteroids, calcineurin inhibitors, crisaborole ointment, and phototherapy (if prescribed). Patients are often obligated to do step therapy with an off-label drug such as cyclosporine or methotrexate for 3 months, and they need to demonstrate responses with objective measures of severity such as the SCORAD (SCORing Atopic Dermatitis) and the validated Investigator Global Assessment.

"Most of my patients carry insurance that does not approve dupilumab without failure of a prior off-label systemic immunosuppressant medication," Kirkorian said. Cyclosporine is her first choice for a systemic immunosuppressant "because it has a fast onset of action, it's effective for treatment of atopic dermatitis, and safe for short-term use," she said. "I don't think that methotrexate works well for eczema. It can take weeks and weeks to work."

She typically starts patients on a 5 mg/kg dose of cyclosporine. Baseline tests include CBC, CMP (comprehensive metabolic panel), lipids, and vitals. She repeats the labs at 1 month, and includes a blood pressure check. Potential adverse effects of cyclosporine include infections (including opportunistic infections), cytopenias, hypertension, nephrotoxicity, hepatotoxicity, neurotoxicity (including posterior reversible encephalopathy syndrome), electrolyte disturbance, lymphoma, and cutaneous malignancy.

"The good news is that we generally don't see the adverse effects with short-term use," Kirkorian said. "We will see some hypertrichosis and gingival hypertrophy, which resolves with cessation of therapy. There are serious side effects if you use it for long enough."

As for methotrexate, "it is still a very important drug in pediatric dermatology, particularly in other conditions such as psoriasis," she said. "The problem is that weekly dosing of methotrexate poses a greater risk of dosing errors. People aren't really triggered to think of a once-weekly medication. If you do use it, give them a short supply to make sure that they come back, and that they don't give it daily accidentally."

Practical tips she offered for prescribing cyclosporine include supplying a patient handout with information on all adverse effects, dosing information, vaccination information, and pregnancy precautions, with contact information (a patient portal or on-call number) for the treating clinician in case a patient develops adverse effects. Administration of live vaccines while patients are on cyclosporine is not recommended.

When transitioning patients from cyclosporine or methotrexate to dupilumab, Kirkorian recommends tapering the immunosuppressant dose by half every 2 weeks to complete cessation by week 8 of treatment. For patients who experience a severe baseline flare once the immunosuppressant is tapered, despite the switch to dupilumab, she recommends restarting methotrexate at a full dose and then reducing the dose every 2 weeks until the lowest effective dose (2.5-5 mg weekly) is reached.

"Waning efficacy is real," she said. "We can add methotrexate to recapture efficacy. Check for superimposed allergic contact dermatitis."

With upadacitinib (Rinvoq), an oral Janus kinase (JAK) inhibitor recently approved for treating refractory, moderate to severe AD in patients 12 years of age and older, is the risk profile acceptable to parents and physicians? "I think the answer is yes," Kirkorian said. "But we're going to have to think through that very carefully. It's going to be exciting to see how this drug changes management in our patients."

Kirkorian disclosed that she is a member of the advisory board for Verrica Pharmaceuticals.

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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