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

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.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 3: nomenclature and outcome assessment.

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.

What's new in atopic eczema? An analysis of systematic reviews published in 2016. Part 1: treatment and prevention.

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.

What's new in atopic eczema? An analysis of systematic reviews published in 2015. Part 2: prevention and treatment.

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.

What's new in atopic eczema? An analysis of systematic reviews published in 2015. Part 1: epidemiology and methodology.

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 15 systematic reviews that were published during 2015, and focuses on the epidemiology and methodology issues of AE. For systematic reviews on the prevention and treatment of AE, see Part 2 of this update. The worldwide prevalence of AE during childhood has been calculated to be 7.89% (95% CI 7.88-7.89), based on studies of 1 430 329 children from 102 countries. Children with AE are four times more likely than controls to have allergic rhinitis and asthma [relative risk (RR) = 4.24, 95% CI 3.75-4.79]. Twin studies show the heritability of AE to be about 75%. AE is more prevalent in patients with vitiligo and alopecia, and is positively associated with a high body mass index in America and Asia but not in Europe. Possible relationships between AE and exercise, maternal folate supplementation, maternal stress and autism spectrum disorder (ASD) have been assessed, but more high-quality studies are needed for definitive conclusions. The Harmonising Outcomes Measures for Eczema (HOME) Initiative is developing a core set of outcome measures for AE trials. Suitable instruments for measuring quality of life are yet to be agreed, and use of Investigator Global Assessment in trials requires standardization. Transparent reporting of AE trials remains problematic.

What's new in atopic eczema? An analysis of systematic reviews published in 2014. Part 2. Treatment and prevention.

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 12 systematic reviews (SRs) that were published or indexed during 2014, and focuses on the treatment and prevention of AE. For an update of SRs on the epidemiology, mechanisms of disease and methodological issues, see Part 1 of this update. Although phototherapy and various systemic medications (including ciclosporin, azathioprine and methotrexate) are commonly used to treat AE, many of these have not been robustly assessed in head-to-head randomized controlled trials. Educational interventions may improve AE severity and quality of life for children and their families. Intake of probiotics prenatally and postnatally may help prevent AE, but there is little evidence to suggest a role in the treatment of AE. Although no benefit was found for allergen avoidance in preventing AE, the use of immunotherapy to treat AE-associated aeroallergen sensitivity requires further evaluation. There is insufficient evidence for Vitamin D supplementation for the treatment of AE This overview of reviews provides a succinct guide for clinicians and patients wishing to remain up to date with the most recent evidence for the treatment and prevention of AE.

What's new in atopic eczema? An analysis of systematic reviews published in 2014. Part 1. Epidemiology, risk factors and outcomes.

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.

Observational, longitudinal study of delirium in consecutive unselected acute medical admissions: age-specific rates and associated factors, mortality and re-admission.

OBJECTIVES: We aimed to determine age-specific rates of delirium and associated factors in acute medicine, and the impact of delirium on mortality and re-admission on long-term follow-up. DESIGN: Observational study. Consecutive patients over two 8-week periods (2010, 2012) were screened for delirium on admission, using the confusion assessment method (CAM), and reviewed daily thereafter. Delirium diagnosis was made using the Diagnostic and Statistical Manual Fourth Edition (DSM IV) criteria. For patients aged ≥65 years, potentially important covariables identified in previous studies were collected with follow-up for death and re-admission until January 2014. PARTICIPANTS: 503 consecutive patients (age median=72, range 16-99 years, 236 (48%) male). SETTING: Acute general medicine. RESULTS: Delirium occurred in 101/503 (20%) (71 on admission, 30 during admission, 17 both), with risk increasing from 3% (6/195) at <65 years to 14% (10/74) for 65-74 years and 36% (85/234) at ≥75 years (p<0.0001). Among 308 patients aged >65 years, after adjustment for age, delirium was associated with previous falls (OR=2.47, 95% CI 1.45 to 4.22, p=0.001), prior dementia (2.08, 1.10 to 3.93, p=0.024), dependency (2.58, 1.48 to 4.48, p=0.001), low cognitive score (5.00, 2.50 to 9.99, p<0.0001), dehydration (3.53, 1.91 to 6.53, p<0.0001), severe illness (1.98, 1.17 to 3.38, p=0.011), pressure sore risk (5.56, 2.60 to 11.88, p<0.0001) and infection (4.88, 2.85 to 8.36, p<0.0001). Patients with delirium were more likely to fall (OR=4.55, 1.47 to 14.05, p=0.008), be incontinent of urine (3.76, 2.15 to 6.58, p<0.0001) or faeces (3.49, 1.81-6.73, p=0.0002) and be catheterised (5.08, 2.44 to 10.54, p<0.0001); and delirium was associated with stay >7 days (2.82, 1.68 to 4.75, p<0.0001), death (4.56, 1.71 to 12.17, p=0.003) and an increase in dependency among survivors (2.56, 1.37 to 4.76, p=0.003) with excess mortality still evident at 2-year follow-up. Patients with delirium had fewer re-admissions within 30-days (OR=0.32, 95% CI 0.09 to 1.1, p=0.07) and in total (median, IQR total re-admissions=0, 0-1 vs 1, 0-2, p=0.01). CONCLUSIONS: Delirium affected a fifth of acute medical admissions and a third of those aged ≥75 years, and was associated with increased mortality, institutionalisation and dependency, but not with increased risk of re-admission on follow-up.

Awareness of and attitudes towards skin-cancer prevention: a survey of patients in the UK presenting to their general practice.

BACKGROUND: The rate of skin cancer in the UK continues to rise. AIM: To identify the current knowledge and awareness of and attitudes towards the avoidance of skin cancer among a variety of patient groups to aid the design of future UK sun-awareness campaigns. METHODS: Patients aged ≥ 16 years presenting to one of three general practices (two urban, one rural) in the UK during the period 1 June to 31 July 2010 were invited to complete a paper-based questionnaire collecting data on their sun-exposure behaviour, with significance assessed by the Fisher exact test. RESULTS: In total, 1000 patients (327 male, 673 female) responded. Those aged 16-30 years were significantly more likely to get sunburn than the older age groups. The understanding of ways to avoid skin cancer in 16-30-year-olds was also rated as significantly worse than that of all other age groups. Compared with the older age groups, this group was also less likely to avoid midday sun exposure (P < 0.001) or to cover up in the sun (P < 0.001). There was no significant difference in sun exposure or frequency of sunburn between those with or without a personal or family history of skin cancer. Those with a positive history were more likely to wear sunscreen (P < 0.01), but not to cover up or avoid the midday sun. CONCLUSIONS: UK-based sun-awareness programmes should target younger age groups. In addition, healthcare professionals must ensure that opportunities are taken to reinforce the importance of safe sun exposure for patients presenting with skin cancer.

Common filaggrin null alleles are not associated with hymenoptera venom allergy in Europeans.

The association of filaggrin mutations with atopic eczema (atopic dermatitis, AD) is well established and it is thought that filaggrin dysfunction impairs the skin's barrier function allowing allergen penetration and subsequent cutaneous sensitisation and inflammation. However, as most forms of barrier dysfunction are not associated with allergic sensitisation to common allergens, the possibility that filaggrin itself is involved in Th1/Th2 polarisation remains. We tested the hypothesis that allergen delivered to the skin independently of the stratum corneum is not associated with filaggrin mutations. Wasp stings bypass the stratum corneum and deliver antigen to the dermis. We found that European individuals with AD (n = 32) have an increased frequency of the 2 commonest filaggrin null mutations (R501X and 2282del4) compared to those with vespid allergy (n = 56) and healthy controls (n = 30). Thus, filaggrin does not appear to have a downstream effect on the development of allergic disease, and it is indeed filaggrin's role in the epithelial function that is likely to determine the link between filaggrin mutations and allergic sensitisation.

Filaggrin null mutations associate with increased frequencies of allergen-specific CD4+ T-helper 2 cells in patients with atopic eczema.

BACKGROUND: Filaggrin null mutations associate with atopic eczema and also with asthma when present with eczema. However, while epidermal dysfunction is an important factor in disease pathogenesis, it is unclear how such dysfunction interacts with immune responses to contribute to cutaneous and other inflammatory atopic disease. OBJECTIVES: To gain a better understanding of the mechanisms underlying such predisposition in order to understand different disease phenotypes and possibly identify potential treatment targets. METHODS: We studied 33 individuals with atopic eczema and used interleukin-4 immunospot and human leucocyte antigen class II tetrameric complexes to investigate the peripheral blood allergen-specific CD4+ T-cell responses. RESULTS: Filaggrin null mutations associated with significantly (P<0·05) higher frequencies of allergen-specific CD4+ T-helper 2 cell responses. CONCLUSIONS: These data would support a model where barrier dysfunction possibly promotes greater allergen penetration and delivery to drive allergen-specific CD4+ T cells. This could further contribute to respiratory and cutaneous inflammatory disease.