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IntroductionAtopic dermatitis is a complex disease with differing clinical presentations. Many attempts have been made to identify uniform subtypes, or phenotypes, of atopic dermatitis in order to identify different aetiologies, improve diagnosis, estimate more accurate clinical prognoses, inform treatment andmanagement or predict treatment efficacy andeffectiveness. However, no consensus yet exists on exactly what defines these phenotypes or how many there are and whether they are genuine or statistical artefacts. This review aims to identify previously reported phenotypes of atopic dermatitis, the features used to define them and any characteristics or clinical outcomes significantly associated with them.Methods and analysisWe will search Ovid Embase, Ovid MEDLINE and Web of Science from inception to the latest available date at the time of the search for studies attempting to classify atopic dermatitis in humans using any cross-sectional or longitudinal epidemiological or interventional design. Primary outcomes are atopic dermatitis phenotypes, features used to define them and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. Two reviewers will independently screen titles and abstracts for inclusion, extract data and assess study quality. We will present the results of this review descriptively and with frequencies where possible.Ethics and disseminationEthical approval is not required for this study as it is a systematic review. We will report results from this systematic review in a peer-reviewed journal. The main value of this study will be to inform further research.Prospero registration numberCRD42018087500.

Summary: This review is part of an annual evidence update on atopic eczema (AE), providing a summary of key findings from 18 systematic reviews published in 2019 on AE risk factors and prevention. Parental atopy, particularly AE, is a risk factor for offspring AE, and this risk is augmented both by the number of parental atopic diseases present and the number of affected parents. Low‐quality evidence suggests that autumn or winter birth increases childhood AE risk compared with birth in spring. There is some evidence to support filaggrin gene–environment interactions; however, this is limited by small underpowered studies. There is no evidence to suggest that polymorphisms in the –1082, –592 and –819 loci of the interleukin‐10 gene increase susceptibility to AE. There is no robust evidence to support a relationship between childhood AE development and either yoghurt consumption in the first year of life, gut microbiota variants, prenatal or infantile paracetamol exposure, maternal antibiotic exposure or air pollution. Three systematic reviews investigated the effect of probiotics given during pregnancy or infancy; although low‐quality evidence suggests benefits of combined probiotics, these studies were limited by significant heterogeneity. No relationship between the age at which complementary food and beverages are introduced and the risk of developing AE in infancy was identified. Consistent evidence showed no relationship between human milk feeding and infant AE development, aside from limited evidence suggesting a protective role in those with atopic heredity. This summary of recent evidence related to AE risk factors and prevention highlights the complex aetiology of AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual evidence updates on atopic eczema (AE), and provides a summary of key findings from systematic reviews (SRs) published or indexed in 2019 related to AE treatment. Several SRs assessed the efficacy of topical corticosteroids (TCS), topical calcineurin inhibitors, topical phosphodiesterase‐4 inhibitors and topical Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway inhibitors. However, there is a lack of good‐quality trials comparing topical treatment agents with TCS, which remain the standard of care for patients with AE. Most of the included trials lack meaningful comparisons as they used vehicle as a comparator. There is also lack of harmonization of outcome measures for AE across studies. Large, well‐designed RCTs are needed to further determine whether any specific emollients offer superior benefit. There is evidence highlighting limited benefit of oral H1 antihistamines as 'add‐on' therapy to topical treatment of eczema. Mycophenolate mofetil may have a role in patients with refractory AE. Among biologic therapies, most of the efficacy data relate to dupilumab. Furthermore, there is growing evidence for the efficacy and safety of systemic JAK/STAT pathway inhibitors, but the existing data are of low quality. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Atopic eczema (herein referred to as 'eczema') is a skin disease characterized by remitting and relapsing symptoms. The Harmonising Outcome Measures for Eczema (HOME) initiative was developed to establish a core outcome set (COS) for eczema to be measured for all future eczema trials. The core outcome set for atopic eczema clinical trials includes the domain for patient‐reported eczema control, but a review of the validation of available eczema control instruments was lacking. We aimed to review the literature and systematically assess the measurement properties of validated patient‐reported outcome instruments that capture eczema control. PubMed and Ovid EMBASE were searched up to 24 January 2020 for any study that reported on PROM instrument development or validation. The COnsensus‐based Standards for the selection of health Measurement Instruments (COSMIN) criteria were used to assess the quality of eligible studies. We screened 12 036 titles and abstracts and 58 full texts. A total of 12 papers were included, reporting on seven PROMS. These were assessed with respect to development, reliability, construct validity and responsiveness. Two instruments, Recap of Atopic Eczema (RECAP) and the Atopic Dermatitis Control Tool (ADCT), have been developed and validated to a sufficient standard to support their recommendation as patient‐reported outcome instruments for measuring control of atopic eczema as part of the HOME Core Outcome Set. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of an annual update series on atopic eczema (AE), where systematic reviews (SRs) are gathered and appraised to provide a summary of key recent research findings. The focus of this article is systemic therapies used in AE, while a review on prevention and topical therapies is provided in Part 1. In total, 17 SRs on various systemic treatments used in AE were first published or indexed in 2018. There is a lack of evidence to support vitamin D supplementation, montelukast and naltrexone in AE treatment. The adverse effects of systemic corticosteroids are the main barrier to their use, and there is also a lack of data to determine the optimal delivery and duration of treatment with them. Of other immunosuppressants, ciclosporin has the most robust evidence of efficacy. Biologic therapies in AE treatment are being increasingly investigated, and to date, the greatest quantity of data and evidence of efficacy relates to dupilumab. The most commonly reported adverse effects are injection‐site reactions and conjunctivitis. Other biologics showing some evidence of efficacy include nemolizumab, lebrikizumab and tralokinumab, although further data are needed. There are currently insufficient data on oral small molecules, including Janus kinase inhibitors, in the treatment of AE. A Cochrane review on probiotics showed no significant benefit, and SRs and meta‐analyses on complementary and alternative medicines, including probiotics, in paediatric AE demonstrated significant heterogeneity, thereby limiting their interpretation. This summary of recent SRs provides up‐to‐date evidence for clinicians on systemic therapies in AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review is part of a series of annual updates that summarize the evidence base for atopic eczema (AE). The aim is to provide a succinct guide for clinicians on the key findings from 14 systematic reviews on the prevention and topical treatment of AE published or indexed in 2018. Various supplements, including long‐chain polyunsaturated fatty acids, vitamin D and the probiotic Lactobacillus rhamnosus GG, given prenatally and postnatally, have not been shown to prevent AE in infants, although mixed strains of probiotics may decrease the risk of AE if given to the mother during pregnancy and to the infant for the first 6 months of life. In the postnatal period, there is no evidence that hydrolysed formula, compared with cow's milk formula (CMF), reduces the risk of AE in partially breastfed infants. However, weak evidence suggests that a specific partially hydrolysed whey formula decreases the risk of AE compared with CMF. No specific skin practices can be recommended to reduce the eczema risk in healthy term babies. There is weak evidence of a low risk of reversible hypothalamic–pituitary–adrenal axis suppression following 2–4 weeks of treatment with low‐potency topical steroids, and conflicting evidence as to whether bleach bathing affects skin flora or AE severity. A single study demonstrated that the topical Janus kinase inhibitor tofacitinib at 2% significantly reduces the Eczema Area and Severity Index compared with vehicle. Topical naltrexone cream 1% improves pruritus (measured using a visual analogue scale) by 30% more than placebo. There is weak evidence that topical alternative therapies, including antioxidants, micronutrients and some herbal medicines, may improve AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This article forms part of a series of annual updates that summarizes the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2017, and focuses on the epidemiology, aetiology and risk factors of AE. AE is the largest single contributor to morbidity associated with skin disease worldwide, once mortality has been excluded. There is a high prevalence of sleep disturbance in individuals with AE and they take more sick leave than controls. While there is a lack of skin bacterial diversity in patients with AE, there is a relative abundance of Staphylococcus aureus and Staphylococcus epidermidis. Compared with controls, affected individuals more often show an IgE response to S. aureus antigens and have higher serum interleukin‐31 levels. Early antibiotic exposure, environmental pollutants, maternal atopy and food allergy are associated with an increased risk of AE, and very preterm birth is associated with decreased risk. Patients with AE have a reduced risk of meningioma, but are more likely to develop attention‐deficit hyperactivity disorder compared with controls. Patients with eosinophilic oesophagitis are significantly more likely than unaffected individuals to have AE. There is no significant overall association between AE and allergic contact dermatitis (ACD), and in children referred for patch testing, ACD was more common in those without AE. Hand eczema is more prevalent in patients with AE. There is no association between AE and Type 2 diabetes, hypertension, stroke or myocardial infarction. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It provides a summary of key findings from 25 systematic reviews that were published or indexed during 2017, and focuses on the treatment and prevention of AE. There is high‐quality evidence to demonstrate that dupilumab is better than placebo for the treatment of AE, is not associated with a higher incidence of adverse effects and does not increase the risk of infection compared with placebo; however, comparison studies with other systemic treatments are necessary. Topical tofacitinib is a promising treatment for mild–moderate AE, but currently lacks sufficient evidence from well‐designed randomized controlled trials (RCTs) comparing with other active treatments. Topical doxepin may be effective for pruritus in AE, but available studies have short follow‐up periods and longer‐term outcomes are needed. Bleach baths were no more effective than water baths alone at reducing AE severity. Topical antibiotics cannot be recommended for infected AE, owing to insufficient evidence of benefit. There is little comparison of different emollients in RCTs, but overall evidence indicates that they reduce AE severity, are steroid‐sparing and lead to better outcomes in combination with topical corticosteroids (TCS) than TCS alone. No clear benefit was demonstrated for vitamin D/C/E supplementation in pregnancy for eczema prevention. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review is part of a series of annual updates summarizing the evidence base for atopic eczema (AE). It provides a summary of key findings from 28 systematic reviews that were published or indexed during 2016 with a focus on treatment and prevention of AE. There is reasonable evidence of benefit for topical corticosteroids, calcineurin inhibitors, a glycyrrhetinic acid‐containing preparation (Atopiclair®), oral ciclosporin, oral azathioprine, narrowband ultraviolet B radiation and education programmes. Overall, there is evidence that topical corticosteroids and calcineurin inhibitors have similar efficacy and that both can prevent AE flares when used twice weekly as maintenance therapy. However, topical calcineurin inhibitors are costlier and have more adverse reactions, thus topical corticosteroids should remain the standard of care for patients with AE. There is no evidence that multiple applications are better than once‐daily application of topical corticosteroid. There is inconsistent evidence to support omalizumab and specific allergen immunotherapy use in AE. There is some evidence that vitamin D supplementation and synbiotics reduce AE severity, although the margin of improvement may not be clinically meaningful. There is little evidence to support the use of wet wraps or of complementary/alternative medicine (including Chinese herbal medicine). There is some evidence to suggest that a diet high in fish in infancy may be preventative for AE, but other dietary interventions for the prevention of AE show little promise. This review provides a succinct guide for clinicians and patients wishing to remain up to date with the latest evidence for the treatment and prevention of AE. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE). It presents the key findings from 11 systematic reviews published in 2016 that focus on AE outcome assessment, disease impact and nomenclature. Systematic reviews on the treatment and prevention of AE are summarized in Part 1 of this update, and systematic reviews on the epidemiology of and risk factors for AE are summarized in Part 2. Six reviews summarized what outcome measurement instruments have been used in published AE trials, or summarized validation studies for the available instruments. These reviews were used to inform consensus decisions by the Harmonising Outcome Measures for Eczema initiative. Although validated instruments exist for clinical signs and patient‐reported symptoms, there are currently no validated instruments for capturing quality of life or long‐term control. Four reviews examined the impact of AE on children and their families, but few studies were included. One birth cohort study found no association between AE and educational attainment at 11 years. AE has a moderate impact on health‐related quality of life and a substantial impact on family life. AE is a major risk factor for occupational hand dermatitis, and it is advised that young atopic individuals are informed about high‐risk occupations. Further efforts are required to standardize the nomenclature for AE, which is also commonly known as 'atopic dermatitis' or 'eczema', and preferred terms vary around the world. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE), providing a succinct guide for clinicians and patients. It presents the key findings from 14 systematic reviews published in 2016, focusing on AE epidemiology, aetiology and risk factors. For systematic reviews on the treatment and prevention of AE and for nomenclature and outcome assessments, see Parts 1 and 3 of this update, respectively. The annual self‐reported prevalence of AE is a range of 11.4–24.2%, compared with a general practioner‐diagnosed prevalence of 1.8–9.5%. The mean age of AE diagnosis is 1.6 years. Persistent AE is associated with more severe disease at the time of diagnosis, onset after the age of 2 years and female sex. There is a significant association between having AE and subsequent development of food allergy. Food allergy is also associated with more severe and persistent AE. No consistent association was found between the timing of allergenic food introduction and the risk of developing AE. Evidence from heterogeneous studies indicates that skin absorption is increased in patients with AE, and that there is increased colonization with Staphylococcus aureus in lesional and nonlesional skin and the nasal mucosa of patients with AE compared with controls. There is uncertain evidence indicating an association between AE and smoking exposure, antenatal infection and low maternal vitamin D levels during pregnancy. Weak evidence suggests an increased risk of basal cell carcinoma, but not of melanoma or squamous cell carcinoma, while the risk of glioma is reduced. Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Summary: This review forms part of a series of annual updates that summarize the evidence base for atopic eczema (AE), providing a succinct guide for clinicians and patients. It provides a summary of key findings from 26 systematic reviews that were published during 2015, and focuses on the treatment and prevention of AE. For systematic reviews on the epidemiology and methodological issues, see Part 1 of this update. Topical corticosteroid withdrawal syndrome, ‘steroid addiction’, has been evaluated in a high‐quality systematic review, which helps better define this entity and the risk factors for it. A Cochrane Review has not demonstrated any association between topical corticosteroid use in pregnancy and adverse outcomes, although very large quantities of potent/very potent topical corticosteroids may be associated with reduced birth weight. House dust mite avoidance strategies do not appear to prevent AE. Exposure to probiotics prenatally and in early infancy may help prevent AE, but there is no evidence that maternal diet or supplementation has a preventative effect. [ABSTRACT FROM AUTHOR]

This review summarizes key findings from nine systematic reviews on atopic eczema ( AE) published or first indexed in 2014. It focuses on epidemiology, disease processes and methodological issues. There is reasonable evidence to conclude that high birth weight (> 4000 g) is a risk factor for the development of AE. A lower socioeconomic position is associated with lower prevalence of AE. The effect of exposure to traffic-related air pollution in childhood on the development of AE is uncertain. CD14 polymorphisms do not appear to have an effect in AE. There may be a role for interleukin-18 in AE development. Patients with AE are at decreased risk of brain tumours, but at increased risk of developing attention deficit hyperactivity disorder. Evidence supports the view that normal-appearing skin in AE is in fact structurally abnormal. Lower success rates at inducing remission in AE are associated with increased risk of relapse during long-term follow-up. The Eczema Area Severity Index ( EASI) has been agreed as the preferred core instrument to measure clinical signs in future research. There remains a lack of consensus on the definition of an AE flare. [ABSTRACT FROM AUTHOR]

Background: Many research studies have been published on atopic eczema and these are often summarised in systematic reviews (SRs). Identifying SRs can be time-consuming for health professionals, and researchers. In order to facilitate the identification of important research, we have compiled an on-line resource that includes all relevant eczema reviews published since 2000. Methods: SRs were searched for in MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Database of Systematic Reviews, DARE and NHS Evidence. Selected SRs were assessed against the pre-defined eligibility criteria and relevant articles were grouped by treatment category for the included interventions. All identified systematic reviews are included in the Global Resource of EczemA Trials (GREAT) database (www.greatdatabase.org.uk) and key clinical messages are summarised here. Results: A total of 128 SRs reviews were identified, including three clinical guidelines. Of these, 46 (36%) were found in the Cochrane Library. No single database contained all of the SRs found. The number of SRs published per year has increased substantially over the last thirteen years, and reviews were published in a variety of clinical journals. Of the 128 SRs, 1 (1%) was on mechanism, 37 (29%) were on epidemiology, 40 (31%) were on eczema prevention, 29 (23%) were on topical treatments, 31 (24%) were on systemic treatments, and 24 (19%) were on other treatments. All SRs included searches of MEDLINE in their search methods. One hundred six SRs (83%) searched more than one electronic database. There were no language restrictions reported in the search methods of 52 of the SRs (41%). Conclusions: This mapping of atopic eczema reviews is a valuable resource. It will help healthcare practitioners, guideline writers, information specialists, and researchers to quickly identify relevant up-to-date evidence in the field for improving patient care. [ABSTRACT FROM AUTHOR]

Summary [ABSTRACT FROM AUTHOR]

This review summarizes clinically important findings from nine systematic reviews of the causes, treatment and prevention of atopic eczema (AE) published between August 2008 and August 2009. Two systematic reviews concluded that there is a strong and consistent association between filaggrin ( FLG) mutations and development of eczema. The associations between FLG mutations and atopic sensitization, rhinitis and asthma are weaker than between FLG mutations and eczema, especially if those who also have eczema are excluded. The relationship between transforming growth factor levels in breast milk and eczema development is still unclear. A further systematic review found no strong evidence of a protective effect of exclusive breastfeeding for at least 3 months against eczema, even in those with a positive family history of atopy. Based on a systematic review and meta-analysis of six randomized controlled trials, supplementation with omega-3 and omega-6 oils is unlikely to play an important role in the primary prevention of eczema or allergic diseases in general. There is little evidence to support dietary restrictions of certain foods in unselected children with AE. There is also little evidence to suggest a clinically useful benefit from using probiotics in patients with established eczema. A systematic review of topical pimecrolimus and tacrolimus added little additional information to previous reviews, and did not provide any new data on long-term safety. Both of these drugs work in AE, and may reduce flares and usage of topical corticosteroids; however, there is still uncertainty about how they compare with topical corticosteroids. [ABSTRACT FROM AUTHOR]

This review summarizes clinically important findings from 19 systematic reviews published between January 2006 and August 2007 on the topic of atopic eczema (AE). The evidence suggests that avoidance of allergenic foods during pregnancy or the use of hydrolyzed or soy formula milks does not prevent eczema. Delayed introduction of solids may decrease eczema risk. Asthma typically develops in around a third of children with eczema, and wheezing in early infancy is a predictor of risk. Established topical corticosteroids such as betamethasone should be used just once daily. Topical tacrolimus and pimecrolimus can be used for people who become dependent on topical corticosteroids, especially on sensitive sites such as the face. Wet wraps are useful in secondary care for inducing remission in a child, but they are not a treatment for mild eczema and they should not be used long term. Oral ciclosporin can be used for inducing a remission in severe eczema, and azathioprine can be considered for maintenance treatment. Narrowband ultraviolet (UV)B phototherapy can be used for chronic AE, and UVA1 may be useful for acute eczema. There is little convincing evidence of a clinical benefit with evening primrose oil for eczema, but there is some good new evidence that educational support to eczema families is beneficial. Future trials need to be larger, and include active comparators, patient-reported outcomes and longer-term aspects of disease control. They should be better reported, and registered on a public clinical trials register. [ABSTRACT FROM AUTHOR]