Blood Single-Cell Transcriptomic and Proteomic Signatures of Paradoxical Eczema in Patients with Psoriasis Treated with Biologics

Biologics targeting the TNF and IL-17/23 axis are highly effective treatments for psoriasis but can result in cutaneous adverse events. The pathogenesis of paradoxical eczema, the occurrence of an atopic dermatitis phenotype after biologic initiation in people with psoriasis, is unknown. Using single-cell RNA sequencing and mass cytometry, we found increased expression of TNF, IFN-γ, and IFN-α and their signaling pathways in paradoxical eczema case cell clusters compared with that in matched psoriasis controls. Genetic variants influencing the expression of chemokine signaling and TNF pathway genes were associated with paradoxical eczema in a separate genotyped cohort, and this association was independent of known atopic risk loci. This suggests that paradoxical eczema has a predominantly type 1 systemic inflammatory signature and that genetic susceptibility to aberrant chemokine and TNF pathway signaling could contribute to development of this phenotype during biologic treatment.