Clinical Challenges: Topical Therapy for Atopic Dermatitis in Adults

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease that occurs most frequently in children, but also affects many adults. An estimated 15% of children and 7.3% of adults in the U.S. have been diagnosed with AD.

AD, a form of eczema, can develop on any area of the skin at any age. Adults who have AD often have red to dark patches and scaly skin. They also can have extremely dry skin, hand eczema, eye problems, and skin that is easily irritated. This common skin disease varies widely in severity, and can have a significant impact on a patient’s quality of life, as well as the family unit.

While AD cannot be cured, it can be controlled with proper treatment to help ease symptoms, reduce flare-ups, and prevent it from worsening. Topical therapies remain the mainstay of treatment due to their proven track record and generally favorable safety profile. They can be used individually or in combination with other topical, physical, and systemic treatments.

Because different classes of treatment have different mechanisms of action, combining therapies allows for the targeting of AD via multiple disease pathways. While some treatments are well established such as topical corticosteroids, others are newer and based on recent scientific advancements, such as topical Janus kinase (JAK) inhibitors.

“We anticipate continued expansion of topical biologic therapies, JAK inhibitors, and phosphodiesterase inhibitors,” said Robert Sidbury, MD, MPH, chief of dermatology at Seattle Children’s Hospital. “As the inflammation cascade is complex, there is potential for new drug classes with other mechanisms of action as well.”

Sidbury is co-chair of the American Academy of Dermatology (AAD) Atopic Dermatitis Guideline Workgroup, which in January published updated guidelines of care for the management of AD in adults with topical therapies.

“The guidelines, an update of 2014 guidelines, highlight the scientific progress in the area of AD so we can practice up-to-date medicine,” said AAD Atopic Dermatitis Guideline Workgroup co-chair Dawn Marie R. Davis, MD, of the Mayo Clinic in Rochester, Minnesota. “This guideline set provides new information on topical and systemic therapies, comorbidities, and nuances of AD that is also relevant to the pediatric population.”

Many more topical and systemic therapies have become available since 2014, including biologics and JAK inhibitors. The workgroup developed 11 recommendations that include non-prescription and prescription therapies.

Strong recommendations were made for topical treatments in which the benefits clearly outweigh the risks and burdens to the patient. These recommendations apply to most patients in most circumstances. Strong recommendations were made for the following:

• Moisturizers to help relieve patients’ dry, cracked skin, decrease inflammation, reduce the severity of flare-ups, and increase the time between flare-ups. While moisturizers may be used as monotherapy in some mild cases of AD, they are more often used as part of a comprehensive regimen with pharmacologic treatments. Moisturizers may also help reduce the intense itching of the disease. Various types of moisturizers, including emollients (which help repair the skin barrier), occlusive agents (which create a physical barrier on the skin to help prevent water loss), and humectants (which draw in moisture), are commercially available, each with its own mechanism leading to improved skin hydration.

• Topical calcineurin inhibitors (pimecrolimus 1% cream and tacrolimus 0.03% or 0.1% ointment) reduce inflammation and itching, as well as decrease flare-ups. They are a safe anti-inflammatory option for AD, particularly when there is concern about corticosteroid-related adverse events.

• Topical corticosteroids are commonly used as first-line treatment for patients with AD in all skin regions. Corticosteroids help to relieve itching, decrease inflammation, and can decrease infections. Topical corticosteroids target a variety of immune cells and suppress the release of pro-inflammatory cytokines, and are the most commonly used FDA-approved therapy in AD. More than 100 randomized controlled trials have examined the efficacy of topical steroids in AD. Corticosteroids are effective in acute AD, chronic AD, pruritus due to AD, active disease, and prevention of relapses. High-potency corticosteroids are useful for treating severe disease and flares, and medium-potency corticosteroids can be used for longer courses due to a more favorable adverse event profile.

• Phosphodiesterase-4 inhibitors (crisaborole ointment [Eucrisa]) can reduce inflammation, relieve itching, and decrease infections. The treatment is indicated in mild to moderate disease and is used as an alternative to topical corticosteroids and topical calcineurin inhibitors, and has a favorable safety profile.

• JAK inhibitors (ruxolitinib cream [Opzelura]) can be used in the short term to ease the inflammation and itching of patients with mild to moderate AD. The cream provides rapid and sustained improvements in AD symptoms and is well tolerated.

Sequencing the variety of topical therapies for AD can be complex and depends on many factors, including patient preference, medicine palatability, avoidance of allergens, availability, and cost and insurance coverage.

“Most patients are treated with a topical steroid, followed by a non-steroid, such as a topical calcineurin inhibitor or phosphodiesterase inhibitor,” Davis explained. “Topical therapy also includes following a sensitive skin care regimen and avoiding known irritants and allergens” — mainstays of treatment that should be performed consistently.

The AAD guidelines also provide conditional recommendations for the use of bathing and “wet wrap” therapy. Conditional recommendations apply to most patients, but the most appropriate action may differ depending on individual patient factors.

• Wet wrap therapy uses wet bandages to help hydrate and soothe the skin. This treatment provides a barrier against scratching, helps to decrease redness and inflammation, and can reduce the bacteria on the skin. Wet wrap therapy is an effective option to control AD flares and mitigate recalcitrant disease.

The guidelines also made conditional recommendations against the use of topical antimicrobials, antiseptics, and antihistamines due to the low certainty of evidence.

“These recommendations are based on the latest evidence-based research on the most effective topical treatments for our patients,” said Davis. “These recommended treatments can be used individually or in combination with other treatments.”

Topical medications can be used as monotherapy in mild to moderate disease, or as adjuvants for moderate and severe disease. “For example, a patient may get an excellent response to a systemic therapy, yet need an occasional topical medication if there is a flare,” she said.

“Patient education and empowerment are vital to AD management,” Sidbury said. “We need a paradigm shift in management to be more proactive with the use of advanced therapies to assist patients with management.”