Disease trajectories in childhood atopic dermatitis: an update and practitioner’s guide A.D. Irvine1,2,3 and P. Mina-Osorio4 1Paediatric Dermatology and 2National Children’s Research Centre, Our Lady’s Children’s Hospital, Dublin, Ireland; 3Clinical Medicine, Trinity College Dublin, Dublin, Ireland; 4Regeneron Pharmaceuticals, Inc., Tarrytown, NY, U.S.A. British Journal of Dermatology. DOI: 10.1111/bjd.17766

Lead researchers Prof. Alan D. Irvine Dr. Paola Mina-Osorio

Introduction What’s already known? The complex pathophysiology of atopic dermatitis (AD) translates into a heterogeneous clinical presentation (phenotype) and trajectories of disease progression.

Introduction What’s already known? Although the consensus is that most paediatric patients with AD will eventually “outgrow” the disease or follow the longitudinal trajectory known as the “atopic march”, a significant proportion will develop persistent AD and/or other atopic conditions. No known factors conclusively predict the risk of progression or development of comorbidities.

Objective To synthesise and simplify the epidemiological data from various large cohort studies to identify shared clinically relevant characteristics that could help physicians estimate the risk of disease progression in paediatric patients with AD.

Methods: literature analysed Cohort studies with the following criteria were included: Sample size > 500 patients Paediatric patients with AD Longitudinal studies or long-term studies with more than one cross-sectional data analyses or studies focusing on key questions such as influence of environmental factors or parental history of atopy in the risk of development of comorbid conditions

Methods: challenges There are many challenges to analysing epidemiological data including heterogeneity in data collection methods and the lack of consistency in diagnostic criteria and severity scales: – Use of data-driven approaches to identify patterns in large datasets attempts to address these confounding factors There are also challenges in identifying which patients will “outgrow” their AD and which will develop persistent disease. These include the lack of a standardized definition of “persistence” and the episodic nature of the disease with periods of apparent remission, which can only be captured in longitudinal studies.

Methods: identifying risk factors to help develop a practitioner’s guide We examined data from cohort studies to identify risk factors of disease progression. We also developed a practitioner’s guide with some representative clinical scenarios to advise clinicians on key questions to ask that could help identify, counsel and/or refer infants/children with AD who are at potentially higher risk of disease progression and developing atopic comorbidities.

Results: trajectories of disease progression Most atopic paediatric patients do not follow the “atopic march”; multiple trajectories of disease progression exist. Figure based on Belgrave DC, et al. PLoS Med. 2014;11:e1001748. AD, atopic dermatitis.

Results: practitioner’s guide to factors associated with risk of progression Circled responses to key questions represent the highest risk of disease progression and may warrant referral to a specialist: ALSPAC, Avon Longitudinal Study of Parents and Children; BAMSE, Barn/Children Allergi/Allergy Milieu Stockholm Epidemiologic; EMBASE, Excerpta Medica Database; MAS, Multicenter Allergy Study; MeDALL, Mechanisms of the Development of Allergy; PASTURE, Protection Against Allergy: Study in Rural Environments; PEER, Pediatric Eczema Elective Registry; PIAMA, Prevention and Incidence of Asthma and Mite Allergy; TOACS, The Odense Adolescents Cohort Study; WISC, Wisconsin Birth Cohort Study.

Discussion Although predictors of disease progression are still being investigated, the high level of reproducibility observed across the cohort studies suggests that the risk factors listed in this review are clinically relevant. This could help clinicians estimate the risk of disease progression in paediatric AD patients. Clinicians could then decide if referral to a specialist is needed for further evaluation and follow-up.

Conclusions What does this study add? Recent analyses of large-cohort data of paediatric AD patients have suggested the existence of potentially discrete clusters of patients who present with relatively common AD phenotypes. These studies have shed some light on the factors associated with risk of progression, which are reviewed in this paper. A practitioner’s guide with clinical scenarios is provided that could help clinicians identify patients at high risk of progression and determine whether a patient should be monitored and/or requires specialist referral.

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