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Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease that is characterized by a defective skin barrier function. Recent studies have reported mutations of the skin barrier gene encoding filaggrin in a subset of patients with AD. Objective: We investigated whether reduced filaggrin expression was found in patients with AD who were not carriers of known filaggrin mutations and whether filaggrin expression was modulated by the atopic inflammatory response. Methods: Filaggrin expression was measured in skin biopsies and cultured keratinocytes using real-time RT-PCR and immunohistochemistry. Filaggrin loss-of-function mutations were screened in a total of 69 subjects. Results: Compared with normal skin, filaggrin expression was significantly reduced (P < .05) in acute AD skin, with further reduction seen in acute lesions from 3 European American subjects with AD who were heterozygous for the 2282del4 mutation. This was confirmed by using immunohistochemistry. AD skin is characterized by the overexpression of IL-4 and IL-13. Keratinocytes differentiated in the presence of IL-4 and IL-13 exhibited significantly reduced filaggrin gene expression (0.04 ± 0.01 ng filaggrin/ng glyceraldehyde 3-phosphate dehydrogenase; P < .05) compared with media alone (0.16 ± 0.03). Conclusion: Patients with AD have an acquired defect in filaggrin expression that can be modulated by the atopic inflammatory response. Clinical implications: The atopic immune response contributes to the skin barrier defect in AD; therefore, neutralization of IL-4 and IL-13 could improve skin barrier integrity. [Copyright &y& Elsevier]

Objectives: To compare prevalence and severity of diaper dermatitis (DD) in infants and toddlers (babies) across three countries (China, USA, and Germany), including diapered skin measures and caregiver practices., Methods: A cross-sectional study of 1791 babies (~600 from each country) was recruited at each clinical site. Based on regional toilet-training habits, exclusively diaper-wearing infants were recruited between ages 2-8 months in China and 2-18 months in the USA and Germany. DD was measured, as well as skin pH, transepidermal water loss (TEWL), and relative humidity (RH) in the diapered region. Caregiver habits were collected via a questionnaire and included information on hygienic practices., Results: Diaper dermatitis was highest in the perianal area, followed by the intertriginous, genital, and buttock regions. In general, DD was significantly lower in babies in China, highest in Germany, and intermediate in the USA. This rank ordering of DD by geography was also observed in baby age 2-8 months. The lower DD observed in China was associated with lower skin pH and TEWL on diapered skin and decreased RH in the diaper. Chinese caregivers had the highest rate of prophylactic topical product usage, the most robust cleaning of the diapered area, lack of cleansing after urine-only diaper changes, and Chinese infants spent the least time in an overnight diaper., Conclusions: These data suggest caregiver behaviors including prophylactic use of topical products, thorough cleaning after stooling and reduced time in an overnight diaper are associated with less DD, lower superficial skin pH, and enhanced skin barrier., (© 2019 The Procter & Gamble Company. Pediatric Dermatology published by Wiley Periodicals, Inc.)