PDE4 Inhibitor-Responsive Dermatoses: An Emerging Concept in Dermatology

Many inflammatory skin conditions share mechanistic pathways involving multiple receptors and cytokines. Perhaps there is no better endorsement of this idea than the foundational concept of "steroid-responsive dermatoses." Similarly, targeting the phosphodiesterase 4 (PDE4) enzyme, which exists at the crux of several pathways that contribute to inflammatory skin diseases, offers an avenue by which the pathogenesis of multiple conditions may be interrupted. This suggests that PDE4 inhibitors may assume a similar complementary framework for treating "PDE4 inhibitor-responsive dermatoses." Certain formulations of PDE4 inhibitors (including apremilast, crisaborole, and roflumilast) have undergone rigorous investigation in clinical trials and demonstrated robust efficacy and safety in many dermatologic conditions, achieving United States Food and Drug Administration approval for atopic dermatitis, psoriasis, and seborrheic dermatitis. Herein, we summarize the clinical evidence supporting the emerging concept of "PDE4 inhibitor-responsive dermatoses" and propose that PDE4 inhibition offers an additional pathway to achieving desired clinical outcomes.