Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder characterized by complex interactions among Staphylococcus aureus colonization and immunologic, genetic, and environmental (SAIGE) triggers. Currently, no single therapy comprehensively addresses all triggers and the full spectrum of AD manifestations, highlighting an unmet need for therapies that simultaneously target all components of the disease continuum. An expert panel conducted a structured literature review and developed consensus statements during a meeting in March 2025. The consensus highlighted the triggers and continuum of four interdependent pathological presentations perpetuating disease progression: inflammation, colonization/dysbiosis/infection, xerosis, and pruritus - termed the "four demons". In a phase 2a clinical trial, topical zabalafin hydrogel was shown to reduce inflammation, skin dysbiosis, Staphylococcus aureus colonization/infection, reduce pruritus, and xerosis with minimal adverse effects in patients with mild to moderate AD. Recognizing AD as a Continuum emphasizes the necessity for multi-targeted therapeutic strategies. By addressing the interconnected processes of inflammation, infection, pruritus, and xerosis within the AD Continuum, zabalafin offers a promising therapeutic option for sustained disease control.
Schachner et al. (Mon,) studied this question.