Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort
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Published version
Author(s)
Type
Journal Article
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.
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.
Date Issued
2021-09-01
Date Acceptance
2021-09-01
Citation
British Journal of Dermatology, 2021, 185 (3), pp.526-536
ISSN
0007-0963
Publisher
Oxford University Press
Start Page
526
End Page
536
Journal / Book Title
British Journal of Dermatology
Volume
185
Issue
3
Copyright Statement
© 2021 British Association of Dermatologists
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.
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Subjects
ASTHMA
Dermatology
Life Sciences & Biomedicine
PHENOTYPES
RECOMMENDATIONS
Science & Technology
Publication Status
Published
Date Publish Online
2021-09-01