Phosphodiesterase-4 Inhibition

In this episode of Tea with Dr D, host James Q. Del Rosso, DO, is joined by Christopher Bunick, MD, PhD, and later Lisa Swanson, MD, for a deep look at phosphodiesterase-4 (PDE4) inhibition in dermatology, with a special focus on topical roflumilast.Dr Bunick opens with a primer on the science of PDE4, an enzyme that degrades cyclic AMP (cAMP), an intracellular messenger that regulates anti-inflammatory pathways. In conditions such as atopic dermatitis (AD) and psoriasis, overactive PDE4 leads to reduced cAMP and amplified inflammation. By “gumming up” PDE4, roflumilast restores a more balanced, anti-inflammatory state.He explains why PDE4 inhibition is relevant across multiple inflammatory pathways, including Th1, Th2, and Th17, and why roflumilast has demonstrated stronger efficacy than earlier inhibitors like crisaborole. Molecularly, roflumilast mimics cyclic AMP’s binding to PDE4 across 3 key sites, producing far tighter binding than apremilast and crisaborole, which translates to superior clinical potency.Dr Bunick illustrates this with a case of palmoplantar pustular psoriasis that cleared dramatically within 8 weeks on topical roflumilast after multiple biologic and corticosteroid failures, highlighting its durability and barrier-restoring properties. He and Dr Del Rosso contrast this with the limitations of chronic steroid use, noting that roflumilast supports long-term control without barrier compromise.The discussion also touches on vitiligo, where Dr Bunick shares an early case of repigmentation following roflumilast treatment, suggesting possible cAMP-mediated stimulation of melanogenesis. They highlight the molecule’s innovative aqueous-based formulation, optimized for skin-compatible pH and excellent tolerability.In Part 2, Dr Swanson joins to discuss pediatric use. She reviews the 0.15% cream for AD in patients ≥6 years and the 0.05% cream for ages 2–5, both once-daily, steroid-free options that minimize burning and stinging compared with earlier PDE4 inhibitors. They review clinical data that demonstrate rapid itch relief, strong efficacy across IGA and EASI end points, and sustained control with twice-weekly maintenance.Tune in to hear how PDE4 inhibition, and particularly topical roflumilast, is redefining nonsteroidal therapy across age groups and disease states in dermatology.

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