Increased Risk of Cutaneous and Systemic Infections in Atopic Dermatitis—A Cohort Study

TO THE EDITOR Atopic dermatitis (AD, also known as atopic eczema or eczema), is characterized by skin barrier and immunologic dysfunction. Viral and bacterial superinfection of cutaneous lesions, including eczema herpeticum and Staphylococcus aureus in patients with severe disease is well documented (Ong and Leung, 2016; Weidinger and Novak, 2016). Whether the general population of patients with AD has an increased risk of these and other types of infections because of an impaired skin barrier and/or immunologic dysfunction is unclear. A recent meta-analysis of genomewide association studies identified mutations in genes thought to play roles in the regulation of innate and adaptive immunity, in addition to established barrier function susceptibility loci such as filaggrin (Paternoster et al., 2015). Investigations of skin physiology suggest that differences in barrier function are identifiable very early in infancy and are highly predictive of the development of AD (Kelleher et al., 2015). We therefore hypothesized that individuals who develop AD are at increased risk of infections because of underlying genetically influenced immune and barrier dysfunction. The objective of our study was to determine if there was an association between AD and multiple common cutaneous and noncutaneous infections. We performed a cohort study using The Health Improvement Network, a medical records database that is representative of the UK general population (Seminara et al., 2010). Ethics approval for this study was obtained from The Health Improvement Network Scientific Review Committee and the University of Pennsylvania Institutional Review Board. We included 3,112,617 individuals registered before age 18 years who were followed for a mean of 13.7 years (95% confidence interval 1⁄4 13.6, 13.7). We identified subjects with AD based on the presence of at least one of any of the following diagnostic codes on two different visits, as is common practice in studies of chronic conditions using electronic health data (Herrett et al., 2010): atopic dermatitis and related conditions (M11.00), atopic dermatitis/ AD (M111.00), and atopic dermatitis not otherwise specified (M11z.00). The prevalence of AD was 14.4% (95% confidence interval 1⁄4 14.4e14.4). We examined the prevalence of multiple common cutaneous and noncutaneous infections (warts, dermatophyte infection, impetigo, molluscum contagiosum, otitis media, pneumonia, and streptococcal throat infection; codes available in Supplementary Table S1 online). We found that all of the infectious illnesses we had determined to test a priori were more prevalent in those with AD. Using multilevel mixed-effects logistic regression, we examined the odds of each infectious outcome at any time point and found that the strength of association for cutaneous infections varied from a 55% increased odds of impetigo to a 3-fold increased odds of