Background
Eczema is a major contributor to years lost due to disability worldwide and globally the burden of eczema continues to increase, currently affecting 20% of children in developed countries. Eczema is complex, with varied clinical presentations and different responses to treatment. Traditionally eczema is divided into subtypes with and without allergy; however this approach is suboptimal. The recent discovery of the importance of genes regulating the skin barrier in eczema have led to a major change in understanding why eczema occurs and how it is characterized. Individuals with mutations in filaggrin, a protein essential for skin barrier function, are more likely to have earlier onset, more persistent therapy-resistant disease. The recent trials of dupilumab biological therapy for severe eczema highlighted that despite improvement in eczema with active treatment, only 40% of individuals had clear/almost clear skin at 12 weeks, and responses were not predictable based on allergy or filaggrin status, suggesting that a deeper understanding of disease subtypes is now critical. Failure to identify eczema subtypes limits the development of prevention strategies, as it hinders our understanding of why eczema develops. It also contributes to our current suboptimal treatment strategies for eczema, which rely on intensive topical therapy and broad immunosuppressive therapies for severe disease. If we had better understanding of the different eczema subtypes, (as now exists for asthma), we could determine if different risk factors and treatments are relevant for both the onset and the treatment of these different eczema subtypes. Subtyping eczema is timely given the novel drugs targeting specific pathways currently being developed for eczema treatment
There has been a paradigm shift in how eczema is perceived, from being considered a transient disorder of childhood to an understanding that eczema is a systemic inflammatory disorder. Systemic inflammatory disorders may be associated with adverse health and social outcomes, including cardiovascular disorders and impairment of their educational and occupational attainment. There are emerging signals that eczema may be associated with adverse medical outcomes, including strokes and heart attacks. However current studies are limited by the use of cross-sectional designs or by important differences between people that have eczema and people without eczema that may be associated with adverse outcomes, for example adiposity or treatment effects. Different subtypes of eczema may have differing associations with adverse health and social outcomes and may respond differently to treatments as different biological pathways may mediate disease. This research will determine if adverse effects are associated with eczema overall or restricted to certain disease subtypes. Given the high prevalence of eczema, detecting if people with eczema (or specific subtypes of eczema) are at increased risk of adverse outcomes is critically important as it could rapidly inform prevention and/or screening strategies.
Aims
1. To create a new phenotypic classification of eczema in birth cohort data that may be associated with medical and social outcomes and responses to treatment
2. To determine if people with eczema overall and eczema subtypes specifically have an increased risk of cardiac events and poorer educational attainment, and, if increased risks are detected, to establish the predictors of increased risk
Design and methods
1. I will use available social, family and medical data from a subgroup of participants in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective birth cohort study (N =250 eczema cases; N = 50 controls) to creating a new phenotypic classification of eczema (subtypes) in birth cohort data.
2. I will also use cohort study designs to determine if individuals with eczema and specific subtypes have an increased risk of cardiovascular events. I will do this by looking at the relationship between eczema and cardiometabolic risk factors in ALSPAC
3. I will use data from ALSPAC to determine if individuals with eczema and specific eczema subtypes are at increased risk of poorer educational and occupational attainment and if this is mediated by treatment.