Atopic Dermatitis: The Skin Barrier and Beyond

T. Tsakok; R. Woolf; C.H. Smith; S. Weidinger; C. Flohr


The British Journal of Dermatology. 2019;180(3):464-474. 

In This Article

Abstract and Introduction


Background: Atopic 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.

Methods: This is a narrative review based on a systematic literature search.

Conclusions: Dysregulation 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.


Atopic dermatitis (AD, synonymous with atopic eczema) affects approximately 20% of children and 10% of adults in developed countries,[1] with an impact on quality of life comparable with that of epilepsy or type 1 diabetes.[2] Thus, AD represents a considerable burden both to the individual and to society, with annual costs exceeding £800 million in the U.K. (including direct and indirect costs, adjusted for inflation)[3] and approximately US$5 billion in the U.S.A.[4]

AD remains a clinical diagnosis, although several diagnostic criteria have been developed.[5,6] The disease often presents as pruritic, ill-defined, dry and excoriated patches that can affect any part of the body, but typically show age-related distribution and morphology.7Underlying pathological changes include cutaneous infiltration with immune cells, in particular T lymphocytes, and the development of epidermal oedema ('spongiosis'). AD is also associated with a susceptibility to cutaneous infections, notably by bacteria such as Staphylococcus aureus, as well as certain viruses including herpes simplex.[7] Furthermore, children with AD have a higher prevalence of extracutaneous infections, including streptococcal pharyngitis, respiratory infections, recurrent otitis and urinary tract infections,[8] with recent reports even suggesting a relationship between AD and infective endocarditis.[9]

The complex pathophysiology of AD encompasses genetic risk factors, environmental triggers and dysregulation of innate and adaptive immunity. The traditional paradigm of AD espouses a T helper (Th)2-skewed immune system with exaggerated IgE responses to allergens. However, recent genetic, epidemiological and molecular advances have highlighted skin barrier dysfunction as a common precursor and pathological feature. Genome-wide association studies have identified more than 30 susceptibility loci – of which the strongest are null (loss-of-function) mutations in the gene encoding the epidermal protein filaggrin, which is essential for skin barrier function (Figure 1).[10]

Figure 1.

Genetic susceptibility to atopic dermatitis. Genetic susceptibility identified by genome-wide association studies has indicated components of the epidermal barrier, environmental sensing, immune regulation and tissue response as important aspects of the immunopathogenesis of atopic dermatitis. The strongest association is seen with null mutations in the FLG gene, which encodes the epidermal protein filaggrin.

Current pathophysiological concepts of AD highlight disruption of the epidermal barrier leading to increased permeability of the epidermis, pathological inflammation and percutaneous allergic sensitization.[7] Most novel treatment strategies thus target either the skin barrier or cutaneous inflammation. Furthermore, recent studies aiming to address the skin barrier defect have shown promise in preventing AD, such as early emollient use in high-risk infants.[11,12] This may have broader implications in terms of halting progression of the so-called 'atopic march', thereby preventing development of associated atopic comorbidities, such as asthma.

This article aims to summarize our current understanding of AD pathogenesis, and how this is informing development of novel strategies for treatment and prevention. This narrative review was supported by a systematic search, using keywords including 'eczema', 'atopic dermatitis', 'pathogenesis', 'skin barrier', 'immunology', 'treatment' and 'prevention'.