Abstract
BACKGROUND: Atopic dermatitis (AD) disease activity and severity is highly variable during childhood. Early attempts to identify subtypes based on disease trajectory have assessed AD presence over time without incorporating severity.
OBJECTIVES: To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables.
METHODS: We split data from children in the Avon Longitudinal Study of Parents and Children birth cohort into development and validation sets. To identify subtypes, we ran latent class analyses in the development set on AD symptom reports up to age 14 years. We regressed identified subtypes on nongenetic variables in mutually adjusted, multiply imputed (genetic: unadjusted, complete case) multinomial regression analyses. We repeated analyses in the validation set and report confirmed results.
RESULTS: There were 11 866 children who contributed to analyses. We identified one Unaffected/Rare class (66% of children) and four AD subtypes: Severe-Frequent (4%), Moderate-Frequent (7%), Moderate-Declining (11%) and Mild-Intermittent (12%). Symptom patterns within the first two subtypes appeared more homogeneous than the last two. Filaggrin (FLG) null mutations, an AD polygenic risk score (PRS), being female, parental AD and comorbid asthma were associated with higher risk for some or all subtypes; FLG, AD-PRS and asthma associations were stronger along a subtype gradient arranged by increasing severity and frequency; FLG and AD-PRS further differentiated some phenotypes from each other.
CONCLUSIONS: Considering severity and AD trajectories leads to four well-defined and recognizable subtypes. The differential associations of risk factors among and between subtypes is novel and requires further research.
| Original language | English |
|---|---|
| Pages (from-to) | 526-536 |
| Number of pages | 11 |
| Journal | British Journal of Dermatology |
| Volume | 185 |
| Issue number | 3 |
| Early online date | 2 Mar 2021 |
| DOIs | |
| Publication status | Published - Sept 2021 |
Bibliographical note
Funding Information:This article presents independent research supported by a Wellcome Trust Senior Research Fellowship in Clinical Science to S.M.L. (205039/Z/16/Z) and a National Institute of Arthritis and Musculoskeletal and Skin Diseases Career Development Award to K.A. (K23AR073915). This work was also supported by British Skin Foundation Innovative grant (8066) and Health Data Research UK (LOND1), which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome Trust. It was also supported by the European Research Council under the European Union’s Seventh Framework Programme (FP7/2007‐2013) / ERC grant agreement no 668954. The UK Medical Research Council and Wellcome Trust (grant ref.: 217065/Z/19/Z) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and A.R.M. will serve as guarantor for the contents of this paper.
Funding Information:
sources See Appendix?1 for full details.We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. We also thank Drs Sadia Haider and Toshinori Nakamura at the National Heart & Lung Institute, Imperial College London, for their valuable input into the design of this research.
Publisher Copyright:
© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.