There is a growing desire to explain the worldwide rise in the prevalence of atopic dermatitis (AD). Trend data on the burden of AD suggest that the picture in the developing world may soon resemble ...that of wealthier nations, where AD affects over 20% of children. This, combined with significant variations in prevalence within countries, emphasizes the importance of environmental factors. Many hypotheses have been explored, from the modulation of immune priming by hygiene, gut microbiota diversity, and exposure to endotoxins through farm animals to the effects of pollution, climate, and diet. The discovery of the filaggrin skin barrier gene and its importance in AD development and severity has brought the focus on gene–environment interactions and the identification of environmental factors that impact on skin barrier function. This article reviews our current understanding of the epidemiology of AD, with an emphasis on the findings reported in the international literature over the last 5 years.
Summary
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.
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.
Summary
Background
The Global Burden of Disease (GBD) Study provides an annually updated resource to study disease‐related morbidity and mortality worldwide.
Objectives
Here we present the burden ...estimates for atopic dermatitis (AD), including data from inception of the GBD project in 1990 until 2017.
Methods
Data on the burden of AD were obtained from the GBD Study.
Results
Atopic dermatitis (AD) ranks 15th among all nonfatal diseases and has the highest disease burden among skin diseases as measured by disability‐adjusted life‐years (DALYs). Overall, the global DALY rate for AD in 1990 was 121 95% uncertainty interval (UI) 65·4–201 and remained similar in 2017 at 123 (95% UI 66·8–205). The three countries with the highest DALY rates of AD were Sweden (327, 95% UI 178–547), the UK (284, 95% UI 155–478) and Iceland (277, 95% UI 149–465), whereas Uzbekistan (85·1, 95% UI 45·2–144), Armenia (85·1, 95% UI 45·8–143) and Tajikistan (85·1, 95% UI 46·1–143) ranked lowest.
Conclusions
The global prevalence rate of AD has remained stable from 1990 to 2017. However, the distribution of AD by age groups shows a bimodal curve with the highest peak in early childhood, decreasing in prevalence among young adults, and a second peak in middle‐aged and older populations. We also found a moderate positive correlation between a country’s gross domestic product and disease burden. GBD data confirm the substantial worldwide burden of AD, which has remained stable since 1990 but shows significant geographical variation. Lifestyle factors, partially linked to affluence, are likely important disease drivers. However, the GBD methodology needs to be developed further to incorporate environmental risk factors, such as ultraviolet exposure, to understand better the geographical and age‐related variations in disease burden.
What is already known about this topic?
Atopic dermatitis (AD) is a common skin condition affecting around 20% of children and up to 10% of adults in high‐income countries.
There is a sparsity of studies that have taken a truly global approach, in particular among adult populations.
What does this study add?
We provide the first global map of the burden of AD across age groups, including disability‐adjusted life‐years.
This ranks AD 15th among nonfatal diseases overall and top among skin diseases.
The burden of AD has remained stable between 1990 and 2017, with the highest prevalence rate seen during early childhood and a second rise from middle age.
Plain language summary available online
The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were ...held between December 2020 and July 2021. Twenty‐nine experts (including clinicians and patient representatives) from 12 European countries participated. This first part of the guideline includes general information on its scope and purpose, the health questions covered, target users and a methods section. It also provides guidance on which patients should be treated with systemic therapies, as well as recommendations and detailed information on each systemic drug. The systemic treatment options discussed in the guideline comprise conventional immunosuppressive drugs (azathioprine, ciclosporin, glucocorticosteroids, methotrexate and mycophenolate mofetil), biologics (dupilumab, lebrikizumab, nemolizumab, omalizumab and tralokinumab) and janus kinase inhibitors (abrocitinib, baricitinib and upadacitinib). Part two of the guideline will address avoidance of provocation factors, dietary interventions, immunotherapy, complementary medicine, educational interventions, occupational and psychodermatological aspects, patient perspective and considerations for paediatric, adolescent, pregnant and breastfeeding patients.
Summary
Patients with atopic dermatitis (AD) have an increased risk of bacterial skin infections, which cause significant morbidity and, if untreated, may become systemic. Staphylococcus aureus ...colonizes the skin of most patients with AD and is the most common organism to cause infections. Overt bacterial infection is easily recognized by the appearance of weeping lesions, honey‐coloured crusts and pustules. However, the wide variability in clinical presentation of bacterial infection in AD and the inherent features of AD – cutaneous erythema and warmth, oozing associated with oedema, and regional lymphadenopathy – overlap with those of infection, making clinical diagnosis challenging. Furthermore, some features may be masked because of anatomical site‐ and skin‐type‐specific features, and the high frequency of S. aureus colonization in AD makes positive skin swab culture of suspected infection unreliable as a diagnostic tool. The host mechanisms and microbial virulence factors that underlie S. aureus colonization and infection in AD are incompletely understood. The aim of this article is to present the latest evidence from animal and human studies, including recent microbiome research, to define the clinical features of bacterial infections in AD, and to summarize our current understanding of the host and bacterial factors that influence microbial colonization and virulence.
Summary
The International Psoriasis Council, a global nonprofit organization dedicated to innovation across the full spectrum of psoriasis, led a symposium to discuss the current state of psoriasis ...epidemiology and to introduce the vision and development of a Global Psoriasis Atlas. The symposium was held on 9 September 2015 at the 45th annual meeting of the European Society for Dermatological Research, Rotterdam, the Netherlands. Collectively, these presentations highlighted challenges associated with assessing psoriasis epidemiology and emphasized the urgent need for an authoritative resource to clarify psoriasis disease burden on a global scale.
Summary
Conventional culture‐based studies have suggested that a reduction in microbial exposure in early life predisposes to atopic eczema and allergies. However, molecular microbiological methods ...have shown that conventional culture fails to grow around 80% of the bacterial flora. More recent work reviewed in this paper has employed next generation sequencing to study the influence of the gut and skin microbiota, both with regard to the risk of developing atopic eczema but also the role of pathogenic and commensal bacteria in established disease. Birth cohorts investigating the gastrointestinal tract reported reduced faecal microbiota diversity among those who later developed atopic eczema, using gel electrophoresis, real‐time PCR or 16S ribosomal RNA gene pyrosequencing. However, the inverse association with reduced faecal bacterial diversity was not confirmed in cross‐sectional studies among patients with established atopic eczema. Only two studies investigated the cutaneous microbiota in a longitudinal study design and both were unable to provide evidence that Staphylococcus aureus colonisation precedes the development of atopic eczema. Next generation sequencing has confirmed the cross‐sectional association between atopic eczema and S. aureus colonisation. The two studies that used this approach have also shown that disease flares are associated with a significant fall in skin microbiota diversity and an increase in the relative abundance of both S. aureus and epidermidis. Interestingly, S. aureus elimination does not appear to be the main reason why atopic eczema improves after a flare and antimicrobial and anti‐inflammatory therapy enhances bacterial diversity. Further, well‐phenotyped birth cohorts that take key confounders, such as antibiotic exposure, into account are required.
What's already known about this topic?
Culture‐based studies have shown strong associations between cutaneous Staphylococcus aureus colonisation and established atopic eczema during and outside of the context of disease flares.
Using the same approach, there is also evidence for an inverse relationship between gut bacterial diversity in early life and the later development of atopic eczema, in keeping with the ‘biodiversity hypothesis’.
However, bacterial culture misses around 80% of the bacteria detectable with next generation pyrosequencing.
What does this study add?
16S rRNA sequencing has shown that both Staphylococcus aureus and epidermidis proliferate whilst bacterial diversity drops at lesional sites when atopic eczema flares, but S. aureus elimination is not the main reason why atopic eczema gets better.
Next generation sequencing studies have not found evidence that S. aureus colonisation triggers atopic eczema development, although the current body of literature is very small.
In addition, there is further evidence that a reduced diversity of the faecal microbiota precedes the development of atopic eczema, an association that appears lost in established disease.
The evidence‐ and consensus‐based guideline on atopic eczema was developed in accordance with the EuroGuiDerm Guideline and Consensus Statement Development Manual. Four consensus conferences were ...held between December 2020 and July 2021. Twenty‐nine experts (including clinicians and patient representatives) from 12 European countries participated. This second part of the guideline includes recommendations and detailed information on basic therapy with emollients and moisturizers, topical anti‐inflammatory treatment, antimicrobial and antipruritic treatment and UV phototherapy. Furthermore, this part of the guideline covers techniques for avoiding provocation factors, as well as dietary interventions, immunotherapy, complementary medicine and educational interventions for patients with atopic eczema and deals with occupational and psychodermatological aspects of the disease. It also contains guidance on treatment for paediatric and adolescent patients and pregnant or breastfeeding women, as well as considerations for patients who want to have a child. A chapter on the patient perspective is also provided. The first part of the guideline, published separately, contains recommendations and guidance on systemic treatment with conventional immunosuppressive drugs, biologics and janus kinase (JAK) inhibitors, as well as information on the scope and purpose of the guideline, and a section on guideline methodology.
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