Atopic dermatitis: the skin barrier and beyond

BackgroundAtopic dermatitis is the most common chronic inflammatory skin disorder, affecting up to 20% of children and 10% of adults in industrialized countries. This highly debilitating condition poses a considerable burden to both the individual and society at large. The pathophysiology of atopic dermatitis is complex, encompassing both genetic and environmental risk factors. MethodsThis is a narrative review based on a systematic literature search. ConclusionsDysregulation of innate and adaptive immunity plays a key role; however, recent epidemiological, genetic and molecular research has focused interest on skin barrier dysfunction as a common precursor and pathological feature. Current understanding of the aetiology of atopic dermatitis highlights disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation in the skin, and percutaneous sensitization to allergens. Thus, most novel treatment strategies seek to target specific aspects of the skin barrier or cutaneous inflammation. Several studies have also shown promise in preventing atopic dermatitis, such as the early use of emollients in high-risk infants. This may have broader implications in terms of halting the progression to atopic comorbidities including food allergy, hay fever and asthma. What's already known about this topic? Atopic dermatitis is a common and highly debilitating chronic inflammatory skin disorder. Immune dysregulation plays a key role, but recent evidence has shifted the focus to skin barrier disruption as the key precursor. Loss-of-function mutations in the filaggrin gene are the strongest known genetic risk factor, but there are numerous environmental and immunological factors that influence the disease manifestation and course. The current therapeutic armamentarium is limited to simple lipid-based barrier-enhancing emollients, topical anti-inflammatory agents and systemic immunosuppressive therapies. What does this study add? We review how defects in structural epidermal proteins and environmental factors converge to impair skin barrier function, resulting in increased susceptibility to atopic dermatitis. We explore the impact of the defective skin barrier on immune responses and the skin microbiome, highlighting how the complex interplay between the skin barrier and immune activation determines the response to environmental factors such as allergens and microbes. We outline emerging strategies for treating and preventing atopic dermatitis. Linked Comment: Silverberg. Br J Dermatol 2019; 180:447-448.