Disease trajectories in childhood atopic dermatitis: an update and practitioner's guide

Abstract

Background: Atopic dermatitis (AD) is a heterogeneous disease with a multifactorial aetiology and complex pathophysiology. This heterogeneity translates into different trajectories of disease progression with respect to severity, persistence and risk of development of atopic comorbidities. Determining which possible disease trajectories or comorbidities any individual child might develop is challenging in clinical practice. Tools that help identify paediatric patients at higher risk of disease progression would greatly aid clinicians.

Methods: We reviewed recent cohort studies to synthesize and simplify the epidemiological data to try to identify shared clinically relevant characteristics that may help physicians estimate the risk of disease progression in paediatric patients with AD.

Results: Despite the variability in data collection and methods of analysis and their limitations, there are common patterns of early-childhood AD that may aid in the estimation of risk for disease progression. Factors associated with risk of AD progression include younger age of onset, family history of atopy, greater AD severity, filaggrin mutations, urban environment and polysensitization and/or allergic multimorbidity. Based on these factors, we provide a practitioner's guide for identifying, counselling and/or referring infants and children with AD at potentially higher risk of developing persistent AD and atopic comorbidities. We also present clinical scenarios to illustrate how these data relate to real-life situations.

Conclusions: Useful insights are provided for physicians and patients to inform them better about the risk of AD progression and to help guide care pathways for the paediatric population with AD. What's already known about this topic? The complex pathophysiology of atopic dermatitis (AD) translates into a heterogeneous clinical presentation and trajectories of disease progression. 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. What does this study add? Recent analyses of data from large cohorts of paediatric patients with AD have suggested the existence of potentially discrete clusters of patients who present with relatively common AD phenotypes. These studies have shed some light onto the factors associated with risk of progression, which we review in this article. A practitioner's guide with clinical scenarios is provided to help identify patients at high risk of progression to determine whether a patient should be monitored and/or would require specialist referral.

Figure 1

Atopic dermatitis (AD) has a multifactorial pathophysiology involving genetic and environmental factors leading to immune dysregulation and skin barrier dysfunction. This complexity translates into heterogeneous clinical presentations (phenotypes). The term ‘endotype’ encompasses all these clinical, pathological and aetiological aspects of a disease and has been applied to asthma and other complex diseases to refer to the molecular mechanisms underlying observable disease characteristics (phenotypes).

Figure 2

The atopic march has been defined as the sequential progression from atopic dermatitis to asthma and allergic rhinitis. The common perception is that patients either follow this trajectory or outgrow the disease. This graph shows the percentage of patients with each of the indicated allergic conditions (y‐axis) at different age groups (x‐axis) in the subset of patients who follow what is traditionally known as the atopic march trajectory. This corresponds to the cross‐sectional analysis of the data described by Belgrave et al.41

Figure 3

Despite the different methodologies used in recent data‐driven analyses of cohort data, the characteristics of the patient clusters representing distinct trajectories of disease progression are remarkably similar among studies. We have consolidated the information from the table into four more or less overlapping subsets represented in different shades of red in the concentric circles. AD, atopic dermatitis; ALSPAC, Avon Longitudinal Study of Parents and Children; MAAS, Manchester Asthma and Allergy Study; MAS, Multicenter Allergy Study; MeDALL, Mechanisms of the Development of Allergy; PARIS, Pollution and Asthma Risk: an Infant Study; PASTURE, Protection Against Allergy: Study in Rural Environments; PIAMA, Prevention and Incidence of Asthma and Mite Allergy.

Figure 4

Paediatric patients with atopic dermatitis (AD) can follow multiple trajectories of disease progression. The atopic march represents one of multiple such possible trajectories. Analysing data cross‐sectionally at a population level at any of the indicated time points could result in either under‐ or overestimation of the co‐occurrence of any number of atopic comorbidities studied. The figure is based on the findings described by Belgrave et al.41

Figure 5

A practitioner's guide for identifying paediatric patients with atopic dermatitis who are at risk of disease progression and developing atopic comorbidities. This figure presents the relevant questions to ask in the clinic, which may aid in family counselling and the decision‐making process for the management and/or early referral of paediatric patients with atopic dermatitis. Based on data from the cohorts listed on the left, circled responses to these questions represent the highest risk. Referral to a specialist is recommended for patients with any of these characteristics. ALSPAC, Avon Longitudinal Study of Parents and Children; BAMSE, Children Allergy Milieu Stockholm Epidemiology; 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.