Abstract

Understanding the pathogenesis of many inflammatory skin diseases and their associated signalling pathways has revealed multiple promising therapeutic targets. Given the chronic nature of many of these conditions, products with long-term safety and efficacy are desired. While topical corticosteroids have been the mainstay of topical therapies for years, they are burdened by concerns over long-term safety (i.e., atrophy, striae, telangiectasias), risk of absorption with systemic glucocorticoid side effects, and patient apprehension regarding steroid use. Similarly, topical calcipotriol and retinoids may be ineffective and can cause irritation. Although topical calcineurin inhibitors (i.e., pimecrolimus, tacrolimus) have been approved for atopic dermatitis, their off-label use for many inflammatory conditions may be limited by tolerability issues such as stinging and burning, and lack of effectiveness. The emergence of newer targeted small molecules for topical application, including topical phosphodiesterase-4 inhibitors (PDE4i), topical Janus kinase inhibitors (JAKi), and a therapeutic aryl hydrocarbon modulating agent (TAMA), offer promising new options and will be reviewed here and summarized in Table 1.

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