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Zinc plays a central role in skin integrity via barrier and immune mechanisms and may also be relevant in the pathogenesis of atopic dermatitis (AD). However, little is known about the relationship between zinc and AD. We performed a systematic review to determine (i) the association between zinc levels or zinc deficiency and AD and (ii) the efficacy of oral zinc supplementation in the treatment of AD. We searched PubMed, Scopus, Web of Science and article references for observational studies on zinc levels or zinc deficiency in participants with AD vs. controls and for randomized control trials (RCTs) on zinc supplementation in AD. For observational studies, we calculated pooled standardized mean differences (SMDs) or odds ratios (ORs) along with 95% confidence intervals (CIs) using a random effects model. We included 14 observational studies and two RCTs. The pooled SMD demonstrated significantly lower serum (SMD 0.66, 95% CI 0.21-1.10, P = 0.004), hair (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) and erythrocyte (SMD 0.95, 95% CI 0.38-1.52, P = 0.001) zinc levels in participants with AD compared to controls. Pooled unadjusted data from three studies showed a non-significant increased odds of AD in those with zinc deficiency compared with those without zinc deficiency (OR = 1.50, 95% CI 0.71-3.16, P = 0.28). One RCT of oral zinc supplementation among AD patients with zinc deficiency showed improvement in extent and severity of AD, while another RCT among all AD patients showed no significant improvement. All the studies were of low or moderate quality. We conclude that low serum, hair and erythrocyte zinc levels are associated with AD. However, the poor quality of included studies makes interpretation of these results problematic. High-quality observational studies are needed to confirm the association between low zinc levels and AD, and RCTs are required to evaluate the merit of zinc supplementation for the treatment or prevention of AD.

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BACKGROUND: Several factors are known contribute to hair cortisol concentration (HCC) in adults. However, there is less research on determinants of HCC in children and adolescents. HCC is a valuable tool for medical research pertaining to the hypothalamic-pituitary-adrenal (HPA) axis. This review aims to assess the extent to which established determinants of HCC in adults have been consistently reported in children (birth - 18 years) and to identify determinants of HCC specific to this age group. METHODS: Eligible studies were identified, selected and appraised as per PRISMA-P guidelines and as detailed in our systematic review protocol, registered on PROSPERO (registration number CRD42017056220). In view of contrasting methods and measures, a meta-analysis could not be done but a qualitative synthesis was performed. RESULTS: Thirty-six studies were included in the analysis. Higher HCC is associated with male sex and anthropometry, particularly increased body mass index and waist circumference. There is preliminary evidence to suggest that socio-economic status is inversely related to child HCC, particularly with reference to caregiver education and income. Of note, most of the studies analysing socio-economic variables were performed in relatively equal societies. Hair wash frequency and use of hair products and treatments do not affect HCC when proximal segments of hair are used. There is conflicting evidence regarding the relationship between HCC and age in children and adolescents. Further investigation is required to better delineate if and how the following are associated with HCC in children: hair colour, hair type, exposure to trauma and stressors, psychiatric illness, atopic illness, steroid use (including topical and inhaled steroids) and perinatal variables. CONCLUSIONS: Sex and anthropometry are potential confounders and should be considered for adjustment in hair cortisol research. Hair wash frequency and use of hair products and treatments are not important confounders when proximal hair segments are used. A better understanding of HCC in children in relation to exposure to trauma and stressors is required before it can be used as a biomarker, particularly in terms of vulnerable developmental stages, definition and measurement of stress, and temporal relationship to stressors. Age, SES and other correlates also warrant further investigation.

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Nonmelanoma skin cancer (NMSC) comprises mainly basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). The association between alcohol intake and NMSC has been inconclusive; therefore the objective of this study is to quantify the relationship between alcohol intake and NMSC using meta-analyses. A systematic literature search of PubMed and Embase was performed on 30 October 2016. Eligible articles were case-control or cohort studies that examined alcohol intake and risk of BCC or cSCC and reported relative risks (RRs) with 95% confidence intervals (CIs). Of the 307 articles identified, 13 case-control and cohort studies were included in the systematic review, including 95 241 NMSC cases (91 942 BCC and 3299 cSCC cases). A random-effects model was used to obtain summary RRs and 95% CIs for dose-response meta-analyses. For every 10-gram increase in ethanol intake per day, a positive association was found for both BCC (summary RR of 1·07; 95% CI 1·04-1·09) and cSCC (summary RR of 1·11; 95% CI 1·06-1·16). While there was evidence suggesting a nonlinear association for BCC, it may be due to the sparse data at higher alcohol intake levels. This meta-analysis found evidence that alcohol drinking is positively associated with both BCC and cSCC risk in a dose-dependent manner. These results should be interpreted with caution due to potential residual confounding. Nonetheless, because alcohol drinking is a prevalent and modifiable behaviour, it could serve as an important public health target to reduce the global health burden of NMSC.

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