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.Atopic dermatitis (AD, syn. 'atopic eczema' and 'eczema') is the commonest inflammatory skin disease in children and poses a significant burden on healthcare resources (1-4) and patients' quality of life (1, 5-11). As a consequence, there has been a heightened interest in the identification of environmental risk and protective factors, reflected in a steady increase in the number of publications related to AD epidemiology (Fig. 1). This narrative review appraises our latest insights into the epidemiology of AD and highlights potential areas for future research. Papers were identified, using a systematic MEDLINE search from inception until the end of April 2013, using the Cochrane Collaboration Skin Group search terms for AD in combination with exploded terms for incidence, prognosis, cohort, cross-sectional, and longitudinal studies. A formal systematic review was not possible due to the breadth of the topic and heterogeneity in study methodology. This article is one of two commissioned articles, one focusing on the epidemiology and the other on the prevention of AD. Is AD still on the increase?Some of the most valuable AD prevalence and trend data has come from the International Study of Asthma and Allergies in Childhood (ISAAC) (5,(12)(13)(14). With close to two million children from 106 countries, ISAAC is the biggest and only allergy study that has taken a truly global approach. ISAAC's strength is the use of a uniform validated methodology, including physical examination for flexural dermatitis (Phase Two only), allowing direct comparison of results between pediatric populations and providing invaluable data on the worldwide burden of allergic disease. ISAAC Phases One and Three were set up to examine time trends and showed that where AD among 13-and 14-year-olds was common in Phase One (mainly in high income settings), prevalences did not significantly increase further or even decreased, whereas AD burden continued to rise in most developing country settings (Fig. 2) (15). As for 6-to 7-yearolds, the majorit...

Background The RASopathies are a class of human genetic syndromes caused by germline mutations in genes that encode protein components of the Ras/mitogen-activated protein kinase (MAPK) pathway. Costello syndrome (CS) is a RASopathy caused by mutations in the HRAS gene, a key regulator of signal transduction. Objective To quantify the specific cutaneous phenotype observed in 46 individuals with Costello syndrome with confirmed HRAS mutations Methods This was a cross-sectional study. Dermatologic surveys were designed by the authors and were completed by parents of mutation-positive CS individuals at the Costello Syndrome Family Network (CSFN) conferences in 2007 and 2009. Dermatologic exams were performed by the authors at the CSFN conferences. Results Cutaneous papillomas are reported in 33/46 (71.7%) of participants, with age of onset ranging from infancy to 22 years. Individuals with CS are more likely than patients with cardio-facio-cutaneous syndrome (CFC) to present with cutaneous papillomas (71.7% compared to 4.9%, p<0.001) and palmoplantar keratoderma (76.1% compared to 36.1%, p<0.001). Individuals with CS are less likely than individuals with CFC to present with sparse or absent eyebrows (8.7% compared to 90.2%, p<0.001) or keratosis pilaris (32.6% compared to 80.3%, p=0.001). This study also identified that loose, redundant skin on the hands and feet, “stippled” dermatoglyphs (pachydermatoglyphia) on the fingertips 8/26 (31%), and acanthosis nigricans 17/46 (37%) are frequent features of CS. Conclusions While there is significant phenotypic overlap among syndromes of the Ras/MAPK pathway, individuals with CS are more likely than individuals with CFC syndrome to present with cutaneous papillomas, palmoplantar keratoderma and full eyebrows, and are less likely to present with ulerythema ophryogenes, keratosis pilaris or multiple naevi. The dermatologic features of CS, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signaling in cutaneous paraneoplastic syndromes.

There has been a steep rise in the burden of atopic dermatitis (AD), and up to 20% of children in developed countries now suffer of the disease. At present, treatment at best achieves symptom control rather than cure, and there is a strong need to identify new methods of disease prevention. While earlier approaches focused on allergen avoidance strategies, there has been a clear shift towards attempts to induce tolerance and enhancement of skin barrier function, as skin barrier breakdown plays an important role in AD development. This article reviews the latest developments in the prevention of AD.