BACKGROUND:The efficacy and safety of once-daily roflumilast foam 0.3%, a potent phosphodiesterase 4 inhibitor, has been demonstrated in patients with seborrheic dermatitis (SD). OBJECTIVES:To evaluate long-term effects of roflumilast foam 0.3% in patients with SD. METHODS:A phase II, open-label trial (no. NCT04445987) was conducted in patients (aged ≥ 12 years) with SD who completed a prior roflumilast foam trial or were naïve to roflumilast and vehicle. Patients applied roflumilast foam 0.3% once daily to all affected areas, including the scalp, face, trunk, and intertriginous areas, for 24 or 52 weeks (during the course of the trial, the protocol was amended to extend the duration of treatment from 24 weeks to 52 weeks). The primary endpoints were occurrence of treatment-emergent adverse events (AEs); local tolerability and efficacy (via Investigator Global Assessment [IGA]) were also assessed. RESULTS:Overall, 400 patients participated, among whom 62 were enrolled for 52 weeks. AE rates were low, and ≤ 1.1% reported stinging sensation at the application site at each visit. Durable improvement in signs and symptoms of SD was observed at weeks 24 and 52, with 76.0% and 80.4% of patients, respectively, achieving an IGA of clear or almost clear. CONCLUSIONS:Roflumilast foam 0.3% was well tolerated and improved and/or maintained improvements in signs and symptoms of SD for up to 52 weeks. CLINICALTRIALS: GOV LISTING:NCT04445987.

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.

BACKGROUND:Skin adaptogens are a class of active ingredients that can enhance human adaptation by reducing the deleterious effects of intrinsic and extrinsic stressors. Adaptogens' homeostatic actions enhance the skin's resilience, improving skin health and quality. Most of the investigated and identified adaptogens are botanicals and have relevant applications in dermatology, but their precise mechanism of action (MOA) and classification are yet to be determined. METHODS:Articles related to botanical adaptogens published within the last 20 years were obtained from the Ovid, Cochrane, and PubMed databases. Studies had to include botanicals studied topically on the skin and classified as adaptogens in the paper. The systematic search resulted in 643 articles, and after the selection process, 12 studies were chosen for the systematic review. RESULTS:Twelve scientific papers identified 29 topical adaptogens with capabilities of promoting skin health and cosmesis via homeostatic mechanisms. These papers reviewed the effects of topical adaptogens on photodamage, photoaging, antioxidant activity, antimicrobial activity, inflammation, metabolic activity, hormones, and regenerative effects. We propose an identification and classification system of topical adaptogens. We also list currently identified topical adaptogens in the literature and propose other potential cutaneous adaptogens. CONCLUSION:We have identified 29 skin adaptogens and categorized them based on their MOA: safe, homeostatic, and multitargeted. We propose this classification system as a guide to identify and catalog topical adaptogens in dermatology.