Structural Insights: What Makes Some PDE4 Inhibitors More Effective in Inflammatory Dermatoses.

Psoriasis, seborrheic dermatitis, and atopic dermatitis are chronic inflammatory skin diseases affecting millions of people in the United States and worldwide across the human lifespan. The immune pathways underlying the pathogenesis of these dermatoses include Type I (IFN-γ, TNF-α), Type II (IL-4, IL-5, IL-13), and Type III (IL- 17A/F, IL-22, IL-23) cytokines. These cytokines function downstream of the enzyme phosphodiesterase-IV (PDE4), which makes PDE4 an upstream central regulator of inflammatory dermatoses. PDE4, therefore, is a key drug target for alleviating inflammatory skin diseases. In this brief review, we discuss and simplify into clinically relevant terminology the molecular findings of a 2024 study by Wang et al, which analyzed the structural properties of dermatologic PDE4 inhibitors and thereby provided molecular rationale as to why roflumilast has the greatest potency and is highly efficacious across multiple inflammatory dermatoses.