Association between eczema and major cardiovascular outcomes in population-based studies: a systematic review protocol.

INTRODUCTION: Chronic inflammatory diseases such as eczema (also known as atopic dermatitis) have been inconsistently linked to cardiovascular disease and stroke in both mechanistic and epidemiological studies. There is a need to review the existing epidemiological data examining the association between eczema and major cardiovascular outcomes, including angina, myocardial infarction, coronary revascularisation, heart failure, cardiac arrhythmias, stroke and cardiovascular death, in order to improve our understanding of the comorbidities of eczema. METHODS AND ANALYSIS: We will systematically review population-based studies, including cohort, case-control and cross-sectional studies, reporting on the association between eczema and cardiovascular outcomes. We will search Medline, Embase and Global Health, from their date of inception to April 2017, using a comprehensive search strategy formulated with the help of a librarian. Two reviewers will independently screen titles and abstracts in duplicate, followed by independent data extraction and quality assessment. We will group studies by the cardiovascular outcome under study and synthesise them narratively. If sufficient numbers of homogeneous studies are returned, we will perform meta-analyses to obtain pooled effect estimates. Preferred Reporting Items for Systematic Review and Meta-Analysis will be used to inform the reporting of this study. TRIAL REGISTRATION NUMBER: CRD42017060359

By protecting against cutaneous inflammation, epidermal pigmentation provided an additional advantage for ancestral humans.

Pigmentation evolved in ancestral humans to protect against toxic, ultraviolet B irradiation, but the question remains: "what is being protected?" Because humans with dark pigmentation display a suite of superior epidermal functions in comparison with their more lightly pigmented counterparts, we hypothesized and provided evidence that dark pigmentation evolved in Africa to support cutaneous function. Because our prior clinical studies also showed that a restoration of a competent barrier dampens cutaneous inflammation, we hypothesized that resistance to inflammation could have provided pigmented hominins with yet another, important evolutionary benefit. We addressed this issue here in two closely related strains of hairless mice, endowed with either moderate (Skh2/J) or absent (Skh1) pigmentation. In these models, we showed that (a) pigmented mice display a markedly reduced propensity to develop inflammation after challenges with either a topical irritant or allergen in comparison with their nonpigmented counterparts; (b) visible and histologic evidence of inflammation was paralleled by reduced levels of pro-inflammatory cytokines (i.e., IL-1α and INFα); (c) because depigmentation of Skh2/J mouse skin enhanced both visible inflammation and pro-inflammatory cytokine levels after comparable pro-inflammatory challenges, the reduced propensity to develop inflammation was directly linked to the presence of pigmentation; and (d) furthermore, in accordance with our prior work showing that pigment production endows benefits by reducing the surface pH of skin, acidification of albino (Skh1) mouse skin also protected against inflammation, and equalized cytokine levels to those found in pigmented skin. In summary, pigmentation yields a reduced propensity to develop inflammation, consistent with our hypothesis that dark pigmentation evolved in ancestral humans to provide a suite of barrier-linked benefits that now include resistance to inflammation

Association between eczema and major cardiovascular outcomes in population-based studies: a systematic review protocol.

INTRODUCTION: Chronic inflammatory diseases such as eczema (also known as atopic dermatitis) have been inconsistently linked to cardiovascular disease and stroke in both mechanistic and epidemiological studies. There is a need to review the existing epidemiological data examining the association between eczema and major cardiovascular outcomes, including angina, myocardial infarction, coronary revascularisation, heart failure, cardiac arrhythmias, stroke and cardiovascular death, in order to improve our understanding of the comorbidities of eczema. METHODS AND ANALYSIS: We will systematically review population-based studies, including cohort, case-control and cross-sectional studies, reporting on the association between eczema and cardiovascular outcomes. We will search Medline, Embase and Global Health, from their date of inception to April 2017, using a comprehensive search strategy formulated with the help of a librarian. Two reviewers will independently screen titles and abstracts in duplicate, followed by independent data extraction and quality assessment. We will group studies by the cardiovascular outcome under study and synthesise them narratively. If sufficient numbers of homogeneous studies are returned, we will perform meta-analyses to obtain pooled effect estimates. Preferred Reporting Items for Systematic Review and Meta-Analysis will be used to inform the reporting of this study. TRIAL REGISTRATION NUMBER: CRD42017060359

Classifying atopic dermatitis: protocol for a systematic review of subtypes (phenotypes) and associated characteristics.

INTRODUCTION: Atopic 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 ANALYSIS: We 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 DISSEMINATION: Ethical 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 NUMBER: CRD42018087500

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

OBJECTIVE: To investigate whether adults with atopic eczema are at an increased risk of cardiovascular disease and whether the risk varies by atopic eczema severity and condition activity over time. DESIGN: Population based matched cohort study. SETTING: UK electronic health records from the Clinical Practice Research Datalink, Hospital Episode Statistics, and data from the Office for National Statistics, 1998-2015. PARTICIPANTS: Adults with a diagnosis of atopic eczema, matched (on age, sex, general practice, and calendar time) to up to five patients without atopic eczema. MAIN OUTCOME MEASURES: Cardiovascular outcomes (myocardial infarction, unstable angina, heart failure, atrial fibrillation, stroke, and cardiovascular death). RESULTS: 387 439 patients with atopic eczema were matched to 1 528 477 patients without atopic eczema. The median age was 43 at cohort entry and 66% were female. Median follow-up was 5.1 years. Evidence of a 10% to 20% increased hazard for the non-fatal primary outcomes for patients with atopic eczema was found by using Cox regression stratified by matched set. There was a strong dose-response relation with severity of atopic eczema. Patients with severe atopic eczema had a 20% increase in the risk of stroke (hazard ratio 1.22, 99% confidence interval 1.01 to 1.48), 40% to 50% increase in the risk of myocardial infarction, unstable angina, atrial fibrillation, and cardiovascular death, and 70% increase in the risk of heart failure (hazard ratio 1.69, 99% confidence interval 1.38 to 2.06). Patients with the most active atopic eczema (active >50% of follow-up) were also at a greater risk of cardiovascular outcomes. Additional adjustment for cardiovascular risk factors as potential mediators partially attenuated the point estimates, though associations persisted for severe atopic eczema. CONCLUSIONS: Severe and predominantly active atopic eczema are associated with an increased risk of cardiovascular outcomes. Targeting cardiovascular disease prevention strategies among these patients should be considered

Mixed evidence on the relationship between socioeconomic position and atopic dermatitis: A systematic review.

BACKGROUND: Lower socioeconomic position usually portends worse health outcomes, but multiple studies have found that atopic dermatitis is associated with higher socioeconomic position. The nature of this relationship remains unclear. OBJECTIVE: To systematically review the literature on socioeconomic position and atopic dermatitis and determine whether the association varies by patient or study characteristics. METHODS: A literature search was conducted in the PubMed and Embase databases. Individual-level studies addressing the association between all measures of socioeconomic position and the prevalence or incidence of atopic dermatitis were eligible for inclusion. Two independent reviewers screened all texts and extracted all data for qualitative synthesis. RESULTS: Eighty-eight studies met the inclusion criteria. Of the 88 studies, 42% (37) found a positive association between atopic dermatitis and socioeconomic position, 15% (13) found a negative association, and 43% (38) found a null or inconsistent association. Studies conducted in Europe, among children, and based on self-report of eczema were more likely to find a positive association with socioeconomic position. LIMITATIONS: Studies varied both in terms of the measurement of socioeconomic position and the definition of atopic dermatitis, limiting quantitative synthesis. CONCLUSION: The evidence of a positive association between atopic dermatitis and socioeconomic position is not consistent

Atopic eczema and obesity: a population-based study

Background Atopic eczema is a common chronic inflammatory skin disease. Research suggests an association between atopic eczema and obesity, with inconsistent evidence from European populations. Objectives To explore the association between diagnosed atopic eczema and being overweight or obese, and whether increased atopic eczema severity was associated with higher body mass index. Methods We undertook a cross-sectional analysis within a matched (age, sex, GP practice) cohort of adults with and without a diagnosis of atopic eczema. We used primary care (Clinical Practice Research Datalink Gold) and linked hospital admissions data (1998-2016). We used conditional logistic regression to compare the odds of being overweight or obese (adjusting for confounders and potential mediators) in those with atopic eczema (mild, moderate and severe, and all eczema) to those without. Results We identified 441,746 people with atopic eczema, matched to 1,849,722 without. People with atopic eczema had slightly higher odds of being overweight or obese compared to those without (OR 1.08, 95% CI 1.07, 1.09) after adjusting for age, asthma and socio-economic deprivation. Adjusting for potential mediators (high-dose glucocorticoids, harmful alcohol use, anxiety, depression, smoking) had minimal effect on effect estimates (OR 1.07, 95% CI 1.06, 1.08). We saw no evidence that odds of being overweight or obese increased with increasing atopic eczema severity, and there was no association in people with severe eczema. Conclusion We found evidence of a small overall association between atopic eczema and being overweight or obese. However, there was no association with obesity among those with the most severe eczema. Our findings are largely reassuring for this prevalent patient group that may already have an increased risk of cardiovascular disease