Genetic, Clinical, and Environmental Factors Associated With Persistent Atopic Dermatitis in Childhood
Authors: Sunna Thorsteinsdottir, Jakob Stokholm, Jacob P. Thyssen, Sarah Nørgaard, Jonathan Thorsen, Bo L. Chawes, Klaus Bønnelykke, Johannes Waage, Hans Bisgaard
Journal: JAMA Dermatology (2018)

<h3>Importance</h3> Knowledge about factors associated with persistence of atopic dermatitis (AD) during childhood is sparse. <h3>Objective</h3> To explore heritable, environmental, and clinical factors associated with persistent AD based on 13 years' follow-up of an at-risk birth cohort. <h3>Design, Setting, and Participants</h3> In the Copenhagen Prospective Study on Asthma in Childhood 2000 (COPSAC<sub>2000</sub>) clinical birth cohort study, 411 children born to mothers with asthma were followed up until the age of 13 years at a clinical research unit in Copenhagen, Denmark, from August 1998 to June 2015. Atopic dermatitis was diagnosed prospectively during close clinical follow-up according to the criteria of Hanifin and Rajka. Data were gathered on parental history, social circumstances, and environmental factors through parent interviews. The cohort was followed up with biannual visits to the clinic until the age of 7 years and were seen again at age 13 years. Data were analyzed from August 2015 to January 2018. <h3>Main Outcomes and Measures</h3> Atopic dermatitis was diagnosed using Hanifin and Rajka major and minor criteria, and severity was determined by Scoring Atopic Dermatitis (SCORAD) index, with possible scores from 0 to 83, with higher scores indicating more severe AD. <h3>Results</h3> Of the 411 children in the cohort, 203 (49.4%) were male and 186 (45.3%) were diagnosed with AD before the age of 13 years; 40 of 166 children (24.1%) had persistent AD at the age of 13 years, and 126 (76.0%) experienced remission. Factors associated with persistent AD to age 13 years included heritability, environmental exposures, asthma and allergic sensitization, clinical presentation at the time of diagnosis, the composition of Hanifin and Rajka diagnostic minor criteria, and AD severity according to SCORAD. A higher AD genetic risk score was associated with an increased the risk for persistent AD (multivariable odds ratio [OR], 1.8; 95% CI, 1.1-2.9;<i>P</i> = .02), together with paternal asthma (multivariable OR, 3.7; 95% CI, 1.2-11.5;<i>P</i> = .02); paternal AD (multivariable OR, 6.2; 95% CI, 1.17-23.2;<i>P</i> = .007), and higher social circumstances (multivariable OR, 1.6; 95% CI, 1.0-2.5;<i>P</i> = .05). Particular clinical presentations at time of diagnosis were also associated with specific minor criteria of Hanifin and Rajka (Dennie-Morgan and anterior neck folds, white dermographism, intolerance to wool, itching when sweating, tendency to skin infection, food intolerance, and food allergy) (OR, 2.6; 95% CI, 1.1-6.2;<i>P</i> = .03) as well as increased severity at diagnosis (OR, 1.1; 95% CI, 1.0-1.1;<i>P</i> = .007). <h3>Conclusions and Relevance</h3> In a birth cohort of children at risk for asthma who received close clinical follow-up to age 13 years, known genetic AD risk variants, paternal asthma and AD, high social circumstances, diagnostic minor criteria, and disease severity at onset were associated with persistent AD at age 13 years. These findings may be applied in clinical practice to evaluate the likely disease course for individual patients.