Cohort Studies on 71 Different Adverse Health Outcomes Among People with Atopic Eczema in UK Primary Care Data

Abstract

Introduction: Atopic eczema may be related to multiple subsequent adverse health outcomes, however, high quality evidence is limited. The existing evidence base, encompassing hundreds of studies employing heterogenous approaches to study design, analysis and data management, hinders comparison, and has been slow and expensive to build.

Methods: We conducted 71 cohort studies using primary care electronic health records data from Clinical Practice Research Datalink Aurum (1997 - 2023), with cohort sizes of up to 3.6 million with eczema matched (on age, sex and general practice) to 16.8 million without eczema. Applying an outcome-wide study design and confounding-adjustment strategy, we fitted Cox models, estimating hazard ratios (HRs) for each outcome comparing people with eczema to people without. We also assessed the effect of eczema severity, estimated absolute effects, and conducted a range of sensitivity analyses.

Results: Eczema was associated with outcomes with adjusted HRs (99% confidence intervals) of up to 4.02 (3.95-4.10) for food allergy. We found strong evidence of associations, dose-response relationships (with eczema severity), and large rate differences for several outcomes that are not acknowledged in current guidelines, namely: irritable bowel syndrome (1.31 [1.29-1.33]), oesophagitis (1.26 [1.24-1.27]), gastro oesophageal reflux disease (1.25 [1.24-1.26]), thromboembolic disease (1.25 [1.23-1.27]), obesity (1.22 [1.21-1.23]), gastritis and duodenitis (1.22 [1.20-1.23]) and peripheral neuropathies (1.21 [1.20-1.22]). Associations with larger HRs but lower rate differences included: Hodgkin’s lymphoma (1.83 [1.64-2.04]), Crohn’s disease (1.62 [1.54-1.69]), coeliac disease (1.43 [1.38-1.48]), autoimmune liver disease (1.35 [1.54-1.69]), and ulcerative colitis (1.41 [1.35-1.47]).

Interpretation: We identified several novel strong associations between eczema and adverse health outcomes, including some where individuals with eczema, clinicians, and guideline authors may benefit from increased awareness of these risks. Results closely matched those from previous studies specifically designed to investigate cancer, fracture, cardiovascular and mental illness outcomes, suggesting our approach to studying multiple outcomes produces valid estimates.

Funding: This work was funded by a Wellcome Trust Senior Research Fellowship in Clinical Science (205039/Z/16/Z) awarded to Sinéad M. Langan. Krishnan Bhaskaran is funded by a Wellcome Senior Research Fellowship (220283/Z/20/Z). Helen Strongman is funded by the National Institute for Health Research (NIHR) though an Advanced Fellowship (NIHR301730).

Declaration of Interest: Julian Matthewman, Spiros Denaxas, Krishnan Bhaskaran, and Helen Strongman have no conflicts of interest to report. Anna Schultze is employed on a fellowship sponsored by GSK, unrelated to the current research. Sinéad M. Langan is a co-investigator in a consortium with industry and multiple academic partners (BIOMAP-IMI.eu) but is not in receipt of industry funding. Kathryn E Mansfield has received consultancy fees from AMGEN outside of the current work.

Ethical Approval: The study was approved by the London School of Hygiene & Tropical Medicine Research Ethics Committee (Reference number: 29781). This study is based on data from the CPRD obtained under license from the U.K. Medicines and Healthcare products Regulatory Agency. The data are provided by patients and collected by the National Health Service (NHS) as part of their care and support. The study was approved by the Independent Scientific Advisory Committee (Protocol reference number: 23_002665).

Keywords: eczema, atopic eczema, atopic dermatitis, adverse health outcomes, comorbidities, outcome-wide, pipeline