We searched MEDLINE and the Cochrane Library for reports in English from Jan 1, 2010, to March 31, 2015. We used the search terms “atopic dermatitis”, “atopic eczema”, “childhood eczema”, “infantile eczema”, and “endogenous eczema”. Relevant articles were reviewed, and the most recent ones were preferably cited. Additional reports were identified from the reference lists of selected articles. In general, we gave priority to studies in man for basic scientific research, and to randomised
SeminarAtopic dermatitis
Introduction
The description of atopic dermatitis (also known as atopic eczema) in ancient times already noted its clinical hallmarks—namely, intense itch and inflammatory eczematous lesions.1 Nowadays, atopic dermatitis is one of the most common chronic diseases and affects up to a fifth of the population in developed countries. For many years, it was thought to be the first manifestation of atopy (the familial propensity to become IgE-sensitised to environmental allergens) and the initial step in the so-called atopic march that ultimately leads to asthma and allergic rhinitis. As such, research into pathogenesis, prevention, and treatment focused on systemic abnormalities of humoral and T-cell-mediated immune responses. However, findings from epidemiology and molecular research have questioned a primary role of allergic mechanisms and, although not detracting the importance of immune mechanisms, they have placed the epidermis and its barrier functions at the forefront of research and management efforts.2, 3
Section snippets
Prevalence
Lifetime prevalence has shown a worldwide increase in the past 30 years. In developed countries, it seems to plateau now at 10–20%, whereas it is lower but continues to increase in many developing countries.4, 5 In roughly 60% of cases, the disease manifests during the first year of life (ie, early onset), but it can start at any age.6, 7 The earliest clinical signs are skin dryness and roughness, but eczematous lesions usually do not occur before the second month of life. The course can be
Clinical features and diagnosis
No specific laboratory or histological findings have been reported, and thus the diagnosis relies exclusively on clinical features. Several sets of diagnostic criteria have been developed12—eg, the Hanifin and Rajka criteria, and an empirically derived, simplified version distinguishing essential, common, and associated features (appendix), which are useful in the clinical setting. Essential features are pruritus and eczematous lesions that can be acute, subacute, or chronic (figure 1). The
Frequent complications
The skin of patients with atopic dermatitis is prone to secondary infections, which tend to generalise. S aureus is a leading cause of skin and soft-tissue infections. It is present transiently on healthy skin,22 but permanently colonises patients' skin and frequently provokes an impetiginisation of lesions (figure 3A).23 The progression to infection is often associated with a worsening of the disease. Eczema herpeticum (figure 3B) is a severe widespread skin infection with herpes simplex virus
Effects on patients
Itch, sleep deprivation, and social embarrassment due to visible lesions have substantial effects on the psychosocial wellbeing of patients and their relatives. In children, the effect of atopic dermatitis on health-related quality of life is similar to that of other major childhood disorders such as asthma and diabetes.28 Children and adolescents with atopic dermatitis are also at a roughly 1·5-times increased risk for attention-deficit hyperactivity disorder, which might be driven by sleeping
Effects on society
In the WHO 2010 Global Burden of Disease survey, atopic dermatitis ranked first among common skin diseases with respect to disability-adjusted life-years38 and years lived with a disease.39 These findings show that the disease has an important health effect at a population level, albeit the true burden was probably underestimated because psychosocial effects and comorbidities were not considered. The economic effects have been investigated only in a few studies, which are not readily comparable
Causes and risk factors
The strongest risk factor is a positive family history for atopic diseases, particularly for atopic dermatitis.43 Twin studies suggested a heritability of more than 80%,44 although this percentage might be an overestimation, since gene–gene interaction effects were not considered. Until now, 32 susceptibility loci have been identified through gene-mapping studies, but they explain less than 20% of the estimated heritability.45, 46, 47, 48, 49, 50 The strongest known genetic risk factor is null
Main mechanisms of disease
The two major and converging pathophysiological peculiarities are abnormalities of epidermal structure and function, and cutaneous inflammation due to inappropriate immune responses to antigens encountered in the skin. The primary events and key drivers of the disease are topics of continuing debate;3 however, clearly, skin barrier biology and immune mechanisms closely interact.
The skin is an efficient physicochemical, microbial, and immunological barrier that exerts several protective
Management
Atopic dermatitis cannot be cured at present; thus, the aim of management is to improve symptoms and achieve long-term disease control with a multistep approach, as outlined in national and international guidelines (appendix). The main principles are continuous epidermal barrier repair with emollients, avoidance of individual trigger factors, and anti-inflammatory therapy with topical corticosteroids or calcineurin inhibitors. In severely affected cases, phototherapy or systemic
Prevention
No primary prevention strategy has been established at present. Most interventions tested so far focused on allergen avoidance or immunomodulation,152 but an overview of systematic reviews153 did not report clear evidence for effectiveness of measures such as maternal dietary antigen avoidance during pregnancy and breastfeeding, long-term breastfeeding, hydrolysed protein formulas, soy formulas, omega-3 or omega-6 fatty acid supplementation, and interventions with prebiotics or probiotics.
Unresolved questions
Despite much progress (panel), a synthesis of research findings for atopic dermatitis has proved difficult. Our understanding of the natural history of childhood disease and the factors determining its remission and persistence is incomplete, as is the knowledge on epidemiology and clinical features in adults. Ironically, pathophysiological investigations were mostly done in tissue from (few) adult patients, and the generalisability of these results is unclear. Epidermal dysfunction is
Search strategy and selection criteria
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