Identification of atopic dermatitis subgroups in children from 2 longitudinal birth cohorts - 07/03/18
, Olga E.M. Savenije, MD, PhD b, c, Jon Heron, PhD d, David M. Evans, PhD a, e, Judith M. Vonk, PhD c, f, Bert Brunekreef, PhD g, h, Alet H. Wijga, PhD i, A. John Henderson, MD d, Gerard H. Koppelman, MD, PhD b, c, ∗, Sara J. Brown, MD, FRCPE j, k, ∗Abstract |
Background |
Atopic dermatitis (AD) is a prevalent disease with variable natural history. Longitudinal birth cohort studies provide an opportunity to define subgroups on the basis of disease trajectories, which may represent different genetic and environmental pathomechanisms.
Objectives |
We sought to investigate the existence of distinct longitudinal phenotypes of AD and test whether these findings are reproducible in 2 independent cohorts.
Methods |
The presence of AD was examined in 2 birth cohort studies including 9894 children from the United Kingdom (ALSPAC) and 3652 from the Netherlands (PIAMA). AD was defined by parental report of a typical itchy and/or flexural rash. Longitudinal latent class analysis was used to investigate patterns of AD from birth to the age of 11 to 16 years. We investigated associations with known AD risk factors, including FLG null mutations, 23 other established AD-genetic risk variants, and atopic comorbidity.
Results |
Six latent classes were identified, representing subphenotypes of AD, with remarkable consistency between the 2 cohorts. The most prevalent class was early-onset-early-resolving AD, which was associated with male sex. Two classes of persistent disease were identified (early-onset-persistent and early-onset-late-resolving); these were most strongly associated with the AD-genetic risk score as well as personal and parental history of atopic disease. A yet unrecognized class of mid-onset-resolving AD, not associated with FLG mutations, but strongly associated with asthma, was identified.
Conclusions |
Six classes based on temporal trajectories of rash were consistently identified in 2 population-based cohorts. The differing risk factor profiles and diverse prognoses demonstrate the potential importance of a stratified medicine approach for AD.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, eczema, environmental, genetic, latent class analysis, PIAMA, ALSPAC
Abbreviations used : AD, ALPSAC, FLG, LLCA, OR, PIAMA
Plan
| This work and L.P. were supported by a UK Medical Research Council Fellowship (MR/J012165/1). L.P. and D.M.E. work in the Medical Research Council Integrative Epidemiology Unit at the University of Bristol, which is supported by the Medical Research Council and the University of Bristol (MC_UU_12013/4). D.M.E. is supported by an Australian Research Council Future Fellowship (FT130101709). S.J.B. holds a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z). The UK Medical Research Council and the Wellcome Trust (grant reference 102215/2/13/2) and the University of Bristol provide core support for the Avon Longitudinal Study of Parents and Children. The Prevention and Incidence of Asthma and Mite Allergy birth cohort was funded by the Netherlands Organization for Health Research and Development, the Netherlands Organization for Scientific Research, the Lung Function of the Netherlands, the Netherlands Ministry of Spatial Planning, Housing, and the Environment, and the Netherlands Ministry of Health, Welfare, and Sport. |
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| Disclosure of potential conflict of interest: L. Paternoster's institution received a grant from the Medical Research Council for this work. A. J. Henderson's institution received a grant from the Medical Research Council and the Wellcome Trust. G. H. Koppelman's institution received grants from the Lung Foundation of the Netherlands, TEVA the Netherlands, the UBBO Emmius Foundation, and the TETRI Foundation for other works. S. J. Brown's institution received a grant from the Wellcome Trust for this work; the institution also received consultancy fees from Concept Life Sciences and grants from Tayside Dermatological Research Charity and the Wellcome Trust. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 3
P. 964-971 - mars 2018 Retour au numéro
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