Primary role of barrier dysfunction in the pathogenesis of atopic dermatitis

Based upon the efficacy of recently developed biologics, the pathogenesis of atopic dermatitis (AD) is being attributed once again to the prominent inflammation that occurs in this disorder. Yet, molecular genetics has clearly shown that the aetiology of AD can be attributed to mutations in stratum corneum structural proteins that impact epidermal barrier function, while inflammation instead emerges as a downstream consequence of a sustained, barrier‐driven cytokine cascade. Although several different mutations that compromise barrier function are associated with AD, all of these mutations compromise either the contents or secretion of epidermal lamellar bodies. Therapies directed at specific immune participants, though effective temporarily, inevitably are followed by “rebound flares,” just as occur following glucocorticoid therapy. While occlusive moisturizers dampen inflammation, they do not address the underlying lipid biochemical abnormality in AD, which can be corrected more specifically with topical, physiologic lipid‐based forms of barrier repair therapy (BRT). Accordingly, BRT has been shown to be as effective as topical, mid‐potency steroids for the treatment of moderate‐to‐severe paediatric AD.