Abstract / Summary
Background: Elderly atopic dermatitis (elderly AD) is increasingly recognized as a chronic inflammatory skin disorder with immunopathological features that may differ from those in younger populations. Age-related chronic low-grade inflammation (inflammaging) may contribute to this phenotype, but its relationship with immune dysfunction and disease chronicity remains incompletely understood.
Objective: To systematically review and meta-analyze associations between inflammation-related biomarkers and disease severity in older adults with AD and to organize the findings within a hypothesis-generating conceptual framework of immune dysfunction.
Methods: PubMed and the China National Knowledge Infrastructure (CNKI) were searched from inception through December 15, 2025, without language restrictions. Reference lists of eligible reports were also screened. Two reviewers independently screened records, extracted data, and assessed methodological quality using the Joanna Briggs Institute critical appraisal checklist for analytical cross-sectional studies. Correlation coefficients analyses were conducted in R version 4.4.1 using the metafor package, with manual calculations in Microsoft Excel. DerSimonian-Laird random-effects models were used when statistical or prespecified clinical or methodological heterogeneity made a common-effect assumption inappropriate. Otherwise, fixed-effect models were used. The findings were also organized descriptively into four proposed pathophysiological stages.
Results: Six studies met the inclusion criteria and were included for quantitative synthesis. A meta-analysis revealed significant positive correlations between disease severity and serum total IgE, eosinophils, IL-4, and IL-17 levels. Among these biomarkers, eosinophil levels showed the most consistent association with disease severity across studies, whereas cytokines involved in Th2 and Th17 pathways showed considerable heterogeneity. Pathological stage-oriented integration analysis provides a proposed conceptual model that an inflammaging-related low-grade inflammatory milieu may coexist with Th2-polarized responses, aberrant Th17-axis activation, impaired skin-barrier repair, and AD persistence.
Conclusion: Older adults with AD may exhibit multidimensional immune dysregulation beyond a simple late-life continuation of typical AD. Our findings support a hypothesis-generating conceptual framework in which inflammaging is associated with Th2-skewed responses, aberrant Th17 activation, and impaired skin-barrier repair. This framework requires validation in prospective studies but may inform future personalized therapeutic research.