Different definitions of atopic dermatitis: impact on prevalence estimates and associated risk factors

Abstract

Background: There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD), and no uniform clinical definition.

Objectives: To investigate to what extent operational definitions of AD cause fluctuation in the prevalence estimates and the associated risk factors.

Methods: We first reviewed the operational definitions of AD used in the literature. We then tested the impact of the choice of the most common definitions of 'cases' and 'controls' on AD prevalence estimates and associated risk factors (including filaggrin mutations) among children aged 5 years in two population-based birth cohorts: the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford. Model performance was measured by the percentage of children within an area of clinical indecision (defined as having a posterior probability of AD between 25% and 60%).

Results: We identified 59 different definitions of AD across 45 reviewed studies. Of those, we chose four common 'case' definitions and two definitions of 'controls'. The prevalence estimates using different case definitions ranged between 22% and 33% in MAAS, and between 12% and 22% in Ashford. The area of clinical indecision ranged from 32% to 44% in MAAS and from 9% to 29% in Ashford. Depending on the case definition used, the associations with filaggrin mutations varied, with odds ratios (95% confidence intervals) ranging from 1·8 (1·1-2·9) to 2·2 (1·3-3·7) in MAAS and 1·7 (0·8-3·7) to 2·3 (1·2-4·5) in Ashford. Associations with filaggrin mutations also differed when using the same 'case' definition but different definitions of 'controls'.

Conclusions: Use of different definitions of AD results in substantial differences in prevalence estimates, the performance of prediction models and association with risk factors. What's already known about this topic? There is no objective test that can unequivocally confirm the diagnosis of atopic dermatitis (AD) and no uniform clinical definition. This results in different definitions utilized in AD studies, raising concerns on the generalizability of the results and comparability across different studies. What does this study add? This study has shown that different definitions of 'cases' and 'controls' have major impacts upon prevalence estimates and associations with risk factors, including genetics, in two population-based birth cohorts. These findings suggest the importance of developing a consensus on AD definitions of both 'controls' and 'cases' to minimize biases in studies.

Figure 1

Overlap of each definition for current atopic dermatitis (AD) in the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford cohorts. Definition 1: physician‐confirmed AD. Definition 2: physician‐confirmed AD and parent‐reported chronic itchy skin condition affecting skin creases. Definition 3: parent‐reported chronic itchy skin condition affecting skin creases. Definition 4: physician‐confirmed AD or parent‐reported chronic itchy skin condition affecting skin creases. ^aThree children had missing values in definitions 1 and 2.

Figure 2

Performance of prediction models for four different ‘case’ definitions of atopic dermatitis (AD) in the Manchester Asthma and Allergy Study (MAAS) and Asthma in Ashford cohorts. Definition 1: physician‐confirmed AD. Definition 2: physician‐confirmed AD and parent‐reported chronic itchy skin condition affecting skin creases. Definition 3: parent‐reported chronic itchy skin condition affecting skin creases. Definition 4: physician‐confirmed AD or parent‐reported chronic itchy skin condition affecting skin creases. Multivariate logistic regression analysis included filaggrin mutations, parental history of AD, allergic sensitization at age 5 years and physician‐confirmed asthma at age 5 years as predictors. The area of clinical indecision represents the percentage of children whose posterior probability lies between 25% and 60% or 25% and 50%.