Topicals for Atopic Dermatitis: Optimizing Treatment Before Systemic Therapy

With the arrival of effective and safe systemic therapies, new topicals that can help reduce the use of corticosteroids, and ongoing research into investigational agents, the atopic dermatitis treatment paradigm is continuing to change. 

In this interview, Dr Amy Paller shares findings from a recent paper in which she reviewed available agents for atopic dermatitis and offered insight into how to optimize topical management before transitioning to systemic therapy. 

What inspired your research into the topical management of atopic dermatitis?

I see many patients with atopic dermatitis. I am a practicing pediatric dermatologist, and it is one of the most common skin problems in children. We now know 7% of adults also have atopic dermatitis, so it is not uncommon in the adult world either. Atopic dermatitis is a life-altering problem in which patients are so itchy that it affects their wellbeing, sleep, and mental health.

Topical management is how we treat most patients with atopic dermatitis. Two-thirds of patients have mild disease, and only one-third have moderate to severe involvement. Therefore, understanding topical management is of critical importance for this very common problem. It is not just important for the dermatologist with expertise, but also for the primary care provider, allergist, and other clinicians who care for children and adults.

Can you describe your study, including its design and methods?

In a recent paper published in Annals of Allergy, Asthma & Immunology, we looked at optimizing topical management of atopic dermatitis. This is important because most patients are managed not by dermatology or allergy experts, but rather by primary care providers.

The mainstay of treatment continues to be topical corticosteroids, but during the last several years, new topical agents have become available for treating atopic dermatitis, and more are coming down the road. Of course, we also have some systemic therapies available, and more on the way, to treat our patients with moderate to severe atopic dermatitis.

This was a review of what is available in terms of topical management. It gets into some new agents and provides tips that we hope will make it easier for providers to understand what to use depending on the patient’s history, experiences, and severity of disease.

What were your key findings, especially regarding a stepwise approach to treatment?

First, many patients with atopic dermatitis have comorbidities, particularly allergic comorbidities but sometimes others like mental health issues. As such, it takes a multidisciplinary team to make the right diagnosis, provide education, and, most importantly, manage the various aspects of atopic dermatitis and its comorbidities.

We need to make sure we are not just throwing a treatment regimen at patients, but that we understand the situation holistically. If we are talking about a pediatric patient, that means the situation for the entire family.

To consider the optimal regimen that builds on the patient’s history, we need to understand what that patient has been using, what has or has not worked, and what the issues are for that particular patient and family. This requires addressing potential noncompliance, identifying environmental triggers or allergens, and recognizing if there is coexistent infection or contact allergy. And, of course, we must manage other issues like mental health concerns that very much can impact patient’s ability to respond to medications.

Topical steroids are still the cornerstone of therapy. The price is right compared to a lot of newer topical options. In addition, topical corticosteroids have a range of potencies that allows us to treat anything from the smallest affected baby to adults with extensive body involvement, and anything from mild disease to very severe disease.

There is a lot of fear about the use of topical corticosteroids. Nobody gets side effects from acutely and aggressively treating with topical corticosteroids for a relatively short period—for example, a 2-week period with once or twice daily use. The issues we see with topical steroids, most commonly skin thinning, atrophy, stretch marks, or striae, are from chronic use. Therefore, it is common for me to start even babies with a fairly potent topical corticosteroid and use that for 2 weeks without fail to get the disease under control.

The art in topical management is what you do for maintenance because you must individualize treatment and ensure you select a therapy that is safe and that the patient will adhere to.

For a patient who needs to use a treatment day in and day out to maintain control, it may not be practical from a safety standpoint to continue with the topical corticosteroid. In my practice, this is where nonsteroidal agents primarily come in.

For those with moderate to severe disease, we may have to advance from the use of topicals on a chronic basis to a systemic therapy that will allow more intermittent or localized use than topical corticosteroids.

For more than 20 years now, topical calcineurin inhibitors have been available as a steroid sparing agent. I have used them extensively to minimize the chronic use of topical corticosteroids in patients who can access topical calcineurin inhibitors. Fortunately, it is possible to get topical calcineurin inhibitors that are inexpensive; for example, patients can get tacrolimus 0.1% ointment for less than $40 for a 30-gram tube.

When topical calcineurin inhibitors first arrived, we did not understand their long-term safety. When given systemically, tacrolimus can have an immunosuppressive effect, and risks associated with this include a peculiar type of lymphoma. A black box warning was issued in 2006 for this entire class, and it remains today. But after more than 20 years and extensive longitudinal registries tracking the safety of these agents, there is no increased risk of lymphoma or nonmelanoma skin cancer related to calcineurin inhibitors when they are used topically. We can use these agents even in sensitive areas for long periods of time and not see any issues other than potential local burning, stinging, or irritation.

Other new topical agents are available now. Crisaborole is a topical phosphodiesterase-4 inhibitor and has been helpful as a steroid sparing agent for many patients, although it can also cause stinging and burning. Most recently, the first topical Janus kinase inhibitor, called topical ruxolitinib, has become available as well. Its use is restricted to 20% body surface area or less because we want to ensure there is not systemic absorption through topical use, but that does cover a lot of body area.

There are other agents in development right now, such as phosphodiesterase-4 inhibitors and a therapeutic aryl hydrocarbon receptor modulating agent called tapinarof.

We are going to see others arrive in the future, but right now, we already have a strong armament of topical agents that are available for treating atopic dermatitis. It would behoove any practitioner who sees patients with atopic dermatitis, whether children or adults, to become familiar with optimizing topical management, including the use of topical corticosteroids and these newer agents.

And the final concept that has become so important in managing patients with any disease is that of shared decision making. It is critical that any decisions about management are made jointly with the family or patient, so that everybody is on board and patients can adhere to treatment optimally. That is a critical portion of making our therapies work.

Where do you see the future of care headed as more treatments are developed and approved?

The future is very bright for our patients with atopic dermatitis, with these additional topical agents coming out and the availability of safe systemic agents. Dupilumab, for example, is a biologic that is so safe that we do not even do laboratory monitoring, and the only side effect we really see is conjunctivitis in a minority of patients.

This has allowed me to think more readily and earlier on about moving to a systemic agent for many children who have moderate to severe atopic dermatitis. In the past, parents and I have been hesitant about using immunosuppressants due to their frequent laboratory monitoring and the potential for short- and long-term risks.

This is just the tip of the iceberg. Much more will arrive in the future, for both children and adults, and I am greatly looking forward to what lies ahead.

About Dr Paller

Amy S Paller, MD, is the Walter J Hamlin professor, chair of dermatology, and a professor of pediatrics at Northwestern University Feinberg School of Medicine and the Ann & Robert H Lurie Children's Hospital of Chicago. Dr Paller has been researching atopic dermatitis for decades and has been the principal investigator of approximately 75 clinical trials. She has also authored hundreds of articles about atopic dermatitis.