Elsevier

The Lancet

Volume 396, Issue 10247, 1–7 August 2020, Pages 345-360
The Lancet

Seminar
Atopic dermatitis

https://doi.org/10.1016/S0140-6736(20)31286-1Get rights and content

Summary

Atopic dermatitis is a common inflammatory skin disorder characterised by recurrent eczematous lesions and intense itch. The disorder affects people of all ages and ethnicities, has a substantial psychosocial impact on patients and relatives, and is the leading cause of the global burden from skin disease. Atopic dermatitis is associated with increased risk of multiple comorbidities, including food allergy, asthma, allergic rhinitis, and mental health disorders. The pathophysiology is complex and involves a strong genetic predisposition, epidermal dysfunction, and T-cell driven inflammation. Although type-2 mechanisms are dominant, there is increasing evidence that the disorder involves multiple immune pathways. Currently, there is no cure, but increasing numbers of innovative and targeted therapies hold promise for achieving disease control, including in patients with recalcitrant disease. We summarise and discuss advances in our understanding of the disease and their implications for prevention, management, and future research.

Introduction

Atopic dermatitis, also known as eczema and atopic eczema, is one of the most common inflammatory disorders, affecting up to 20% of children and 10% of adults in high-income countries.1, 2 Globally, the prevalence of atopic dermatitis is increasing, although estimates in high-income countries are stabilising. The disorder is characterised by intense itching and recurrent eczematous lesions and has a heterogeneous clinical presentation.3 Although atopic dermatitis can occur at any age, the usual age of onset is in early childhood, typically at age 3–6 months. Evidence suggests that atopic dermatitis in adults is common, including both persistent and new-onset forms.4, 5

The causes of atopic dermatitis are complex and multifactorial. There is a strong genetic component, with evidence for multiple mechanisms of genetic risk. Loss-of-function mutations in the gene encoding filaggrin (FLG) are the most strongly and consistently reported genetic variants, supporting a key role for the skin barrier, as filaggrin is a major structural protein in the epidermis.6 Although genetics are clearly important in atopic dermatitis, the increasing global prevalence of the disorder highlights the role of environmental factors. Individuals with atopic dermatitis are at increased risk of having asthma, allergic rhinitis, and food allergy, and could be at increased risk of a wide range of health and psychosocial outcomes.3

In this Seminar, we aim to discuss major developments in the understanding of atopic dermatitis causes and long-term outcomes and to summarise the rapid expansion of therapeutic options, including targeted therapies.

Section snippets

Clinical signs

Atopic dermatitis is difficult to define because of its great heterogeneity in terms of clinical features, severity, and course. Without definitive tests, clinical signs are needed for diagnosis; a clinician's assessment is considered the gold standard.7 To aid diagnosis, several sets of criteria have been developed. While the UK Working Party criteria9, 10 are widely used for epidemiological studies of children, the Hanifin and Rajka criteria8 and an empirically derived, simplified version,

Epidemiology

Atopic dermatitis affects up to 20% of children and 10% of adults in high-income countries, based on annual self-reported prevalence estimates.3, 8, 23 In 2010, 230 million people worldwide were estimated to have eczema, with reports that the condition was the non-fatal skin disorder with the highest disease burden.24 Data on disease severity are scant but, in a multinational survey, 10–20% of adult patients with atopic dermatitis reported severe disease.25 In a population-based study from the

Natural history

Although the incidence of atopic dermatitis peaks during infancy, there has been a shift from thinking of atopic dermatitis as a resolving early childhood disease to an understanding that atopic dermatitis can have heterogeneous trajectories.38, 39 Patterns described in published work are varied and there is no consensus on optimal identification of subgroups. Trajectories can range from early transient disease to relapsing–remitting atopic dermatitis, chronic persistent atopic dermatitis, or

Pathophysiology and mechanisms of disease

The pathophysiology of atopic dermatitis involves a complex interplay between a dysfunctional epidermal barrier, skin microbiome abnormalities, and a predominantly type-2-skewed immune dysregulation (figure 2A, B).48, 49 These mechanistic drivers can promote and interact with others. For example, skin barrier weakness attributable to a filaggrin deficiency promotes inflammation and T-cell infiltration; colonisation or infection with Staphylococcus aureus damages the skin barrier and induces

Basic management strategies

Atopic dermatitis management aims to improve symptoms and establish long-term disease control. Management plans should be patient-centred and should include avoidance of individual trigger factors, skin barrier restoration using moisturiser, and a step-up and step-down approach aimed at reducing inflammation according to severity of the disease.128, 129, 130, 131, 132 The choice of anti-inflammatory therapy is largely based on disease severity; mild atopic dermatitis can usually be controlled

Health and psychosocial outcomes

Associations between atopic dermatitis and other so-called atopic diseases are well established, including increased risk of asthma, allergic rhinitis, and food allergies, particularly in those with severe and early-onset atopic dermatitis (appendix p 7).24, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 204, 205, 206, 207, 208 Traditionally, the term atopic march was used to describe the evolution from atopic dermatitis to asthma and

Quality of life and costs

The effect of atopic dermatitis on the quality of life of patients, their families, and caregivers is profound and multifaceted (appendix p 7).223 In the 2013 Global Burden of Disease Study, atopic dermatitis was identified as the skin disease with the greatest population-level disability among skin diseases.24 Similarly, the 2013 US National Health and Wellness Survey in adults reported that, among skin diseases, atopic dermatitis has the greatest detriment on skin-disease-specific

Concluding remarks

Atopic dermatitis is one of the most common chronic diseases with a high global burden in health-care costs and morbidity. Although many areas of uncertainty persist (panel 2), discoveries from genetics, molecular biology, epidemiology, and clinical medicine have spurred new disease concepts, including the notion of endotypes, and a broader understanding of health and psychosocial outcomes in atopic dermatitis. In most patients, atopic dermatitis constitutes a lifelong disposition with variable

Search strategy and selection criteria

We searched MEDLINE, the GREAT database, and the Centre of Evidence-based Dermatology web resource of systematic reviews, using the terms “atopic eczema”, “atopic dermatitis”, and “eczema”, in combination with search terms for diagnostic criteria, epidemiology, aetiology, immunology, quality of life, and treatment. Our search focused on articles published in English from January, 2015, to April, 2020. We also included key relevant papers outside this period, such as papers in the reference

References (228)

  • K Abuabara et al.

    Clinical onset of atopic eczema: results from 2 nationally representative British birth cohorts followed through midlife

    J Allergy Clin Immunol

    (2019)
  • EL Simpson et al.

    A pilot study of emollient therapy for the primary prevention of atopic dermatitis

    J Am Acad Dermatol

    (2010)
  • EL Simpson et al.

    Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention

    J Allergy Clin Immunol

    (2014)
  • HO Skjerven et al.

    Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): a factorial, multicentre, cluster-randomised trial

    Lancet

    (2020)
  • SR Wilson et al.

    The epithelial cell-derived atopic dermatitis cytokine TSLP activates neurons to induce itch

    Cell

    (2013)
  • MA McAleer et al.

    The multifunctional role of filaggrin in allergic skin disease

    J Allergy Clin Immunol

    (2013)
  • WH McLean et al.

    Filaggrin variants confer susceptibility to asthma

    J Allergy Clin Immunol

    (2008)
  • SJ Brown et al.

    Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy

    J Allergy Clin Immunol

    (2011)
  • M Pigors et al.

    Exome sequencing and rare variant analysis reveals multiple filaggrin mutations in Bangladeshi families with atopic eczema and additional risk genes

    J Invest Dermatol

    (2018)
  • SJ Brown et al.

    Intragenic copy number variation within filaggrin contributes to the risk of atopic dermatitis with a dose-dependent effect

    J Invest Dermatol

    (2012)
  • J Manz et al.

    Targeted resequencing and functional testing identifies low-frequency missense variants in the gene encoding GARP as significant contributors to atopic dermatitis risk

    J Invest Dermatol

    (2016)
  • MS Elias et al.

    EMSY expression affects multiple components of the skin barrier with relevance to atopic dermatitis

    J Allergy Clin Immunol

    (2019)
  • MD Howell et al.

    Cytokine modulation of atopic dermatitis filaggrin skin expression

    J Allergy Clin Immunol

    (2007)
  • SP Saunders et al.

    Spontaneous atopic dermatitis is mediated by innate immunity, with the secondary lung inflammation of the atopic march requiring adaptive immunity

    J Allergy Clin Immunol

    (2016)
  • EA Kennedy et al.

    Skin microbiome before development of atopic dermatitis: early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year

    J Allergy Clin Immunol

    (2017)
  • P Meylan et al.

    Skin colonization by Staphylococcus aureus precedes the clinical diagnosis of atopic dermatitis in infancy

    J Invest Dermatol

    (2017)
  • JA Geoghegan et al.

    Staphylococcus aureus and atopic dermatitis: a complex and evolving relationship

    Trends Microbiol

    (2018)
  • BH Kaffenberger et al.

    A retrospective descriptive study of oral azole antifungal agents in patients with patch test-negative head and neck predominant atopic dermatitis

    J Am Acad Dermatol

    (2014)
  • K Yoshida et al.

    Distinct behavior of human Langerhans cells and inflammatory dendritic epidermal cells at tight junctions in patients with atopic dermatitis

    J Allergy Clin Immunol

    (2014)
  • JA Odhiambo et al.

    Global variations in prevalence of eczema symptoms in children from ISAAC Phase Three

    J Allergy Clin Immunol

    (2009)
  • K Abuabara et al.

    Patterns and predictors of atopic dermatitis disease control past childhood: an observational cohort study

    J Allergy Clin Immunol

    (2018)
  • K Abuabara et al.

    The prevalence of atopic dermatitis beyond childhood: a systematic review and meta-analysis of longitudinal studies

    Allergy

    (2018)
  • A Sandilands et al.

    Comprehensive analysis of the gene encoding filaggrin uncovers prevalent and rare mutations in ichthyosis vulgaris and atopic eczema

    Nat Genet

    (2007)
  • MP Dizon et al.

    Systematic review of atopic dermatitis disease definition in studies using routinely collected health data

    Br J Dermatol

    (2018)
  • JM Hanifin et al.

    Diagnostic features of atopic dermatitis

    Acta Derm Venereol

    (1980)
  • HC Williams et al.

    Validation of the U.K. diagnostic criteria for atopic dermatitis in a population setting

    Br J Dermatol

    (1996)
  • EE Brenninkmeijer et al.

    Diagnostic criteria for atopic dermatitis: a systematic review

    Br J Dermatol

    (2008)
  • SM Langan et al.

    Clinical features and diagnostic criteria of atopic dermatitis

    (2020)
  • A Torrelo

    Atopic dermatitis in different skin types. What is to know?

    J Eur Acad Dermatol Venereol

    (2014)
  • RM Andersen et al.

    Qualitative vs. quantitative atopic dermatitis criteria - in historical and present perspectives

    J Eur Acad Dermatol Venereol

    (2016)
  • J Schmitt et al.

    Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting

    Allergy

    (2012)
  • EE Grinich et al.

    Standardized reporting of the Eczema Area and Severity Index (EASI) and the Patient-Oriented Eczema Measure (POEM): a recommendation by the Harmonising Outcome Measures for Eczema (HOME) Initiative

    Br J Dermatol

    (2018)
  • B Kunz et al.

    Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis

    Dermatology

    (1997)
  • PI Spuls et al.

    Patient-Oriented Eczema Measure (POEM), a core instrument to measure symptoms in clinical trials: a Harmonising Outcome Measures for Eczema (HOME) statement

    Br J Dermatol

    (2017)
  • HOME website

  • A Lloyd-Lavery et al.

    What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 2: epidemiology, aetiology and risk factors

    Clin Exp Dermatol

    (2019)
  • S Barbarot et al.

    Epidemiology of atopic dermatitis in adults: results from an international survey

    Allergy

    (2018)
  • RJ Silverwood et al.

    Severe and predominantly active atopic eczema in adulthood and long term risk of cardiovascular disease: population based cohort study

    BMJ

    (2018)
  • N Stefanovic et al.

    The exposome in atopic dermatitis

    Allergy

    (2020)
  • Cited by (0)

    View full text