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.

中文翻译：

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两个纵向出生队列儿童特应性皮炎亚组的鉴定

背景

特应性皮炎 (AD) 是一种自然病程各异的常见疾病。纵向出生队列研究提供了根据疾病轨迹定义亚组的机会，这些亚组可能代表不同的遗传和环境病理机制。

目标

我们试图调查 AD 不同纵向表型的存在，并测试这些发现是否可以在 2 个独立队列中重现。

方法

AD 的存在在 2 项出生队列研究中进行了检查，其中包括来自英国的 9894 名儿童 (ALSPAC) 和来自荷兰的 3652 名儿童 (PIAMA)。AD 的定义是父母报告有典型的瘙痒和/或弯曲皮疹。纵向潜在类别分析用于调查从出生到 11 至 16 岁的 AD 模式。我们研究了与已知 AD 风险因素的关联，包括FLG无效突变、其他 23 种已确定的 AD 遗传风险变异以及特应性合并症。

结果

确定了代表 AD 亚表型的 6 个潜在类别，两个队列之间具有显着的一致性。最常见的类型是早发早消型 AD，与男性相关。确定了两类持续性疾病（早发型持续型和早发型晚缓解型）；这些与 AD 遗传风险评分以及个人和父母的特应性疾病史密切相关。鉴定出一类尚未被认识的中期缓解型 AD，与FLG突变无关，但与哮喘密切相关。

结论

在两个基于人群的队列中一致地确定了基于皮疹时间轨迹的六类。不同的危险因素和不同的预后证明了针对 AD 的分层医学方法的潜在重要性。