Four childhood atopic dermatitis subtypes identified from trajectory and severity of disease and internally validated in a large UK birth cohort.
Journal
The British journal of dermatology
ISSN: 1365-2133
Titre abrégé: Br J Dermatol
Pays: England
ID NLM: 0004041
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
pubmed:
4
3
2021
medline:
21
9
2021
entrez:
3
3
2021
Statut:
ppublish
Résumé
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. To identify childhood AD subtypes from symptom severity and trajectories, and determine associations with genetic risk factors, comorbidities and demographic and environmental variables. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33655501
doi: 10.1111/bjd.19885
pmc: PMC8410876
mid: NIHMS1696258
doi:
Substances chimiques
FLG protein, human
0
Filaggrin Proteins
0
Intermediate Filament Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
526-536Subventions
Organisme : Wellcome Trust
ID : 217065/Z/19/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 205039/Z/16/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_19009
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_PC_15018
Pays : United Kingdom
Organisme : NIAMS NIH HHS
ID : K23 AR073915
Pays : United States
Organisme : Medical Research Council
ID : G9815508
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Informations de copyright
© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
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