Systemic Biomarkers Do Not Discriminate Psoriasis, Atopic Dermatitis and Their Coexistence: An Equivalence-Based Cross-Sectional Analysis of 160,782 UK Biobank Participants.

BACKGROUND/

OBJECTIVES

Psoriasis and atopic dermatitis have been conceived as opposite immunological poles, yet molecular overlap and clinically recognised coexistence challenge this dichotomy. We sought to adjudicate among three architectures: overlap with no discriminating systemic signature, a shared inflammatory and metabolic continuum with additive coexistence, and distinct phenotypes with synergy.

METHODS

Cross-sectional analysis of a selected UK Biobank subsample of 160,782 participants, classified by International Classification of Diseases, 10th revision codes L40 and L20 as control, isolated atopic dermatitis (n = 12,859), isolated psoriasis (n = 15,146) and coexistence (n = 1068). Haematological indices, a biochemical and metabolomic panel including glycoprotein acetyls, and circulating inflammatory proteins were evaluated through converging evidence from ordinal effect sizes, equivalence testing at a margin equivalent to an area under the receiver operating characteristic curve of 0.574, quantile regression with interaction terms, permutational multivariate analysis of variance, supervised classification and mixture modelling.

RESULTS

Effect sizes were negligible for 46 of 48 contrasts against a comorbidity-free comparator, and 38 of 48 met formal equivalence. None of the 16 interaction terms survived false discovery rate control. Multivariate separation was detectable but explained 0.6% of dispersion, classification reached an area under the curve of 0.57, and latent classes bore no correspondence to clinical diagnosis. When cardiometabolic exclusions were applied symmetrically to all four groups, every contrast met equivalence, and the ordering of the dominant factor did not persist. Polygenic risk scores confirmed that the coded groups carry the expected genetic architecture.

CONCLUSIONS

Within the systemic biomarkers evaluated these conditions are not discriminable, and coexistence is not an emergent phenotype.