PA09 Persistent barrier dysfunction in lesional atopic dermatitis despite clinical improvement

Abstract

Current assessment of AD severity relies on visual clinical evaluation using the Eczema Area and Severity Index (EASI) and patient-reported outcomes, but tools to make objective measurement of skin barrier function are well established. However, it remains unclear how lesional barrier function correlates with EASI. We compared barrier function in lesional AD before and after systemic therapy. In total, 48 individuals with AD, starting systemic therapy, were recruited to the NOMAD study (Non-invasive and minimally invasive tools to optimise management of atopic dermatitis; funder British Skin Foundation; NRES 23/PR/1301). Corneometer and the transepidermal water loss (TEWL) measurements were taken at skin sites with active eczema (lesional) and nonactive eczema (nonlesional) before and after 16 weeks systemic therapy. At baseline (mean EASI 22.1, SD 14.2), significant differences in barrier function between lesions and nonlesions were confirmed (corneometry P < 0.001; TEWL P < 0.001), but neither correlated with EASI. EASI significantly improved at 16 weeks (mean ΔEASI −14.7, SD 11.3; P < 0.001), but lesional AD did not show significant barrier improvement (corneometer P = 0.79; TEWL P = 0.84; n = 13) and did not correlate with EASI (corneometer P = 0.35, correlation coefficient = 0.020; TEWL lesional P = 0.05, correlation coefficient = 0.086; n = 44). Our data suggest that skin barrier function in individual AD lesions behaves in a stable pathological state, where recovery occurs in a nonlinear manner. Thus, we propose that small reductions in inflammation do not improve barrier function but that this arises once inflammation drops below a critical level. Thus keratinocyte differentiation programmes that regulate barrier function improve rapidly, not gradually. While incompletely clear skin may be an acceptable outcome for some patients, persistent lesions represent ongoing barrier dysfunction and may serve as sites of relapse and antigen exposure. Complete lesion clearance may therefore be a more biologically meaningful target when feasible, particularly in patients with recurrent disease.