The Essential Role of Topical Targeted Therapy in Atopic Dermatitis

Atopic dermatitis (AD) is a chronic inflammatory skin disorder marked by immune dysregulation, epidermal barrier dysfunction, microbiome imbalance, pruritus, and xerosis. Despite therapeutic advances, topical treatments remain the foundation of AD management across all severities. However, most existing topicals address only limited aspects of the disease such as itch or inflammation, resulting in frequent relapse and patient dissatisfaction.

A focused literature review of topical AD therapies published between January 2015 and July 2025 was conducted, emphasizing efficacy and safety. Recent findings were synthesized in this narrative review to highlight the ongoing role of topical treatments in AD management.

AD is a multifactorial condition influenced by Staphylococcus aureus colonization, immune dysregulation, genetic susceptibility, and environmental factors. These contribute to disease pathogenesis, the itch-scratch cycle, and barrier disruption. While systemic therapies are important, AD treatment continues to rely heavily on topical agents. Optimal management should target inflammation, restore barrier function, and address microbiome dysbiosis. Most current treatments focus on individual disease components, with few addressing the full pathogenic spectrum. Emerging evidence on zabalafin (9.5%) hydrogel, a novel botanical topical therapy, suggests potential multi-target benefits, including anti-inflammatory, antipruritic, antimicrobial, and anti-xerotic effects.

There remains a significant unmet need for topical therapies that comprehensively address the AD continuum, including inflammation, itch, barrier dysfunction, and microbial imbalance. Novel agents such as zabalafin may help bridge this gap.  .