Comparison of the Inflammatory Circuits in Psoriasis Vulgaris, Non‒Pustular Palmoplantar Psoriasis, and Palmoplantar Pustular Psoriasis

Palmoplantar pustular psoriasis (PPPP) and non-pustular palmoplantar psoriasis (NPPP) are localized, debilitating forms of psoriasis. The inflammatory circuits involved in PPPP and NPPP are not well understood. To compare the cellular and immunological features that differentiate PPPP and NPPP, skin biopsies were collected from a total of 30 participants with PPPP, NPPP, and psoriasis vulgaris (PV) and from 10 healthy participants. A subset consented to a second biopsy after 3 weeks off medication. Histologic staining of lesional and non-lesional skin showed higher neutrophil counts in PPPP compared with NPPP and PV, and higher CD8+ T-cell counts in NPPP. RNA sequencing and transcriptional analysis of skin biopsies showed enhanced IFN-γ pathway activation in NPPP lesions, but stronger signatures of IL-17 pathway and neutrophil-related genes (e.g. IL36A) in PPPP lesional skin. Serum analysis on the Olink platform detected higher concentrations of T helper (Th) type 1, IFN-γ inducible chemokines in NPPP and higher neutrophil-associated cytokines in PPPP. Taken together, this evidence suggests more pronounced Th1-mediated inflammation in NPPP compared to PV and PPPP, and stronger neutrophil-associated activity in PPPP compared to NPPP and PV. These data support targeting inflammatory pathways associated with neutrophilic inflammation (e.g. IL-36 signaling) for therapeutic development in PPPP.