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PDE4 Inhibitors for Atopic Dermatitis

You may have heard about some of the medications that are available to treat atopic dermatitis, but may be wondering what makes them all different? This article will help to explain topical phosphodiesterase-4 (PDE4) inhibitors, how they work and how patients respond to them.

What are PDE4 Inhibitors?

PDE4 inhibitors are medications that are targeted to treat diseases by changing cell signals in your immune system.1 PDE4 inhibitors work to block cellular pathways in your immune system that can lead to disease flares. When used for atopic dermatitis, these agents target cells in your body that cause inflammatory reactions by reducing specific proteins in your system called cytokines.1

How do they work?

The currently approved PDE4 inhibitor works by blocking an enzyme in your body known as phosphodiesterase-4, (or PDE4).1 This changes your body chemistry and increases a cellular signal chemical known as cyclic adenosine monophosphate (cAMP). The increase of cAMP in your body then suppresses the release of proteins called cytokines that cause inflammation which can lead to atopic dermatitis.2


Currently, there is only one approved PDE4 available in the United States, Eucrisa (crisaborole). This medication comes in an ointment form and is approved for those with mild to moderate atopic dermatitis who are two years old or older.3 This medication is applied twice a day during active flares of atopic dermatitis.2 As of October 2018, there are at least four other topical PDE4 inhibitors currently in active drug trials, and at least one oral PDE4 inhibitor being studied, though there are no expected release dates for these medications yet 1

How do people respond to them?

Patients tend to have an excellent response to the approved PDE4 inhibitor. In a placebo-controlled trial, significantly more patients achieved clear to almost-clear skin using Eucrisa, than the patients on placebo.1,2 Patients also noticed that their skin became less itchy soon after starting Eucrisa, continued to experience relief from their itchiness while on the medication.1

Side effects

Most patients have minimal side effects from PDE4 inhibitors.1,2 The most common side effects are pain and irritation where the medication is applied and sensitivity to the main ingredient in Eucrisa. Most patients apply the medication for four weeks, but the safety of Eucrisa has been evaluated up to 48-weeks, and side effects were
still minimal and the medication was safe for more lengthy use.1 You should not use Eucrisa for extended periods of time without talking to your health care team first to make sure this is the right treatment for you.

Written by Cara King | Reviewed October 2019
  1. Guttman‐Yassky, E,  Hanifin, JM,  Boguniewicz, M, et al.  The role of phosphodiesterase 4 in the pathophysiology of atopic dermatitis and the perspective for its inhibition. Exp Dermatol.  2019; 28: 3– 10.
  2. What are Topical Treatments for Eczema and How Should They Be Used?. National Eczema Association. Published 2019. Accessed April 7, 2019.
  3. Atopic Dermatitis Treatment & Management: Medical Care, Consultations, Diet. Published 2019. Accessed April 7, 2019.