The evolving landscape of phosphodiesterase inhibitors in atopic dermatitis management

INTRODUCTION: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disease associated with recurrent flares, impaired quality of life, and significant psychological burden. Despite therapeutic progress, important unmet needs remain, particularly for steroid-sparing treatments that are safe for long-term use, suitable for sensitive areas, and applicable in pediatric patients. Phosphodiesterase-4 (PDE4) inhibitors represent a targeted anti-inflammatory approach through modulation of intracellular cAMP signaling. AREAS COVERED: This narrative review summarizes current evidence on topical and systemic PDE4 inhibitors in AD. A literature search was performed using PubMed/MEDLINE and ClinicalTrials.gov for studies published up to March 2026. Approved agents such as crisaborole, roflumilast, and difamilast demonstrate moderate efficacy and favorable safety, mainly in mild-to-moderate AD. Emerging therapies, including apremilast, orismilast, and lotamilast, show variable results and remain under investigation. EXPERT OPINION: PDE4 inhibitors have a stable but limited role in AD management. Their main advantages include good tolerability, long-term safety, and suitability for proactive treatment and sensitive skin areas. However, their efficacy is generally lower than that of biologics and JAK inhibitors. Their future role will likely depend on use as adjunctive or personalized therapies rather than replacement of high-efficacy systemic treatments.