Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by life-threatening infections and inflammatory conditions. Hematopoietic cell transplantation (HCT) is the definitive treatment for CGD, but questions remain regarding patient selection and impact of active disease on transplant outcomes. We performed a multi-institutional retrospective and prospective study of 391 patients with CGD treated either conventionally (non-HCT) enrolled from 2004 to 2018 or with HCT from 1996 to 2018. Median follow-up after HCT was 3.7 years with a 3-year overall survival of 82% and event-free survival of 69%. In a multivariate analysis, a Lansky/Karnofsky score <90 and use of HLA-mismatched donors negatively affected survival. Age, genotype, and oxidase status did not affect outcomes. Before HCT, patients had higher infection density, higher frequency of noninfectious lung and liver diseases, and more steroid use than conventionally treated patients; however, these issues did not adversely affect HCT survival. Presence of pre-HCT inflammatory conditions was associated with chronic graft-versus-host disease. Graft failure or receipt of a second HCT occurred in 17.6% of the patients and was associated with melphalan-based conditioning and/or early mixed chimerism. At 3 to 5 years after HCT, patients had improved growth and nutrition, resolved infections and inflammatory disease, and lower rates of antimicrobial prophylaxis or corticosteroid use compared with both their baseline and those of conventionally treated patients. HCT leads to durable resolution of CGD symptoms and lowers the burden of the disease. Patients with active infection or inflammation are candidates for transplants; HCT should be considered before the development of comorbidities that could affect performance status. This trial was registered at www.clinicaltrials.gov as #NCT02082353.

Stress has been associated with atopic dermatitis (AD), however, longitudinal data on the association with AD course are limited. We aimed to examine whether stressful life events are associated with increased AD disease activity and severity throughout childhood using the Avon Longitudinal Study of Parents and Children prospective English birth cohort, comprised of 13,972 children with assessments from birth. The primary exposure was a standardized, age-appropriate scale of stressful life events repeated at 7 times points between ages 1.5 and 8.5. The primary outcome was a repeated measure of AD period prevalence, as defined by caregiver-reported symptoms of flexural dermatitis. The annual period prevalence of AD ranged from 18-21%. For each standard deviation (SD) increase in stressful life events across childhood there was an increased risk of AD activity (OR: 1.07; 95% CI 1.04-1.16), and the association was largest with severe disease (OR 1.13, 95%CI 1.02-1.23). There was no effect modification by the presence of filaggrin gene null mutations or history of asthma or rhinitis. Given the nature of the stressful life events measured, reverse causality is not likely to be an explanation for the results. In a large, prospective, population-based study, we found that stressful life events in childhood confer a small, but significant, risk in increased AD activity and severity. These findings suggest that the impact of stress-reducing interventions should be further investigated in those with AD.

While atopic dermatitis (AD) is known to impact sleep among clinical populations, little is known about the association between AD disease activity and sleep over time among community-based populations. We aimed to determine whether children with active AD have impaired sleep duration and quality compared to children without AD throughout childhood using data from 11,432 individuals in the Avon Longitudinal Study of Parents and Children, a population-based prospective birth cohort in the UK. The annual period prevalence of active AD (assessed by maternal report of a typical itchy flexural rash in the past year, as defined in the International Studies of Asthma and Allergies in Childhood) ranged from 17-33% between infancy and age 15. The primary outcome was a standardized measure of child sleep duration repeated at 10 time points between 0.5-15 years. Multivariate mixed effects regression models with repeated measures of sleep were used to account for the longitudinal nature of the data, and controlled for child gender, race/ethnicity, asthma, number of children living in the household, maternal education, and social class. Throughout childhood, there was no difference in nighttime sleep duration between children with active AD and without AD (p=0.440). In contrast, total sleep duration including napping was higher in younger children with active AD (15 minutes more/day; 95% CI 13-17 minutes; p<.001). Using a composite outcome including nighttime awakenings, early morning awakening, difficulty falling asleep, and nightmares, children with AD were more likely to report worse sleep quality outcomes throughout childhood (OR 1.11; 95% CI 1.05-1.18; p<.001). In conclusion, among the general pediatric population, AD is likely to negatively impact sleep quality more than quantity, which may result in longer naps in early childhood. Clinical outcome measures should differentiate between nighttime and total sleep, and explicitly address sleep quality.

A growing number of studies suggest that prenatal psychological stress promotes atopic disease in offspring, but data on the association with atopic dermatitis (AD) beyond infancy are lacking. We aimed to test whether prenatal psychological stress is associated with an increased risk of AD in offspring using the Avon Longitudinal Study of Parents and Children prospective birth cohort, consisting of 14,879 mother-baby pairs representative of the general population from Bristol, England followed through age 18. The primary outcome was child AD, defined by parent-reported symptoms of flexural dermatitis and clinic visits consisting of skin check by trained personnel conducted at multiple time points. The exposures included prenatal anxiety, depression, and stressful life events weighted by their perceived impact assessed by validated questionnaires during pregnancy. Prenatal depression occurred in 13.57% of mothers, prenatal anxiety occured in 12.63%, and a high perceived impact of stressful life events during pregnancy occurred in 15.78%. After controlling for maternal age, education, social class, smoking, alcohol use, and parental atopic history in Cox proportional hazards regression models, we found that prenatal anxiety and depression were associated with a higher risk of AD: HR for prenatal anxiety 1.19 (95% CI 1.13-1.26), HR for prenatal depression 1.12 (95% CI 1.04-1.21). There was no significant association with perceived impact of stressful life events: HR 1.03 (95% CI 0.98-1.08). Offspring of women who experience high levels of anxiety and depression have a small but significant increased risk of AD and are an important group to target with education and preventative strategies.