Differentiation of Palmoplantar Psoriasis, Palmoplantar Pustulosis and Hyperkeratotic Palmoplantar Eczema Using Proteomic Analysis of Tape Strip Samples.

Palmoplantar inflammatory dermatoses, including hyperkeratotic palmoplantar eczema (HPE), palmoplantar psoriasis (PP) and palmoplantar pustulosis (PPP), present overlapping clinical features that complicate diagnosis and limit targeted therapy. This prospective observational study evaluated whether minimally invasive tape strip sampling, combined with targeted proteomics, can distinguish these conditions at a molecular level. Adults with HPE (n = 14), PP (n = 10), and PPP (n = 12) were enrolled, and tape strips from esional and non-lesional skin were analysed using the Olink Reveal panel (1034 proteins) with validation by MSD multiplex immunoassays. Differentially expressed proteins, pathway enrichment analysis, and protein-protein interaction analyses were conducted across the three diseases, and longitudinal analyses were conducted in a subset of patients with PP. Protein expression patterns showed partial separation of PPP from PP and HPE, whereas PP and HPE overlapped. Lesional samples across all three diagnoses exhibited increased expression of inflammatory proteins compared with non-lesional skin. PPP showed a distinct molecular profile from PP and HPE, with enriched pathways related to neutrophil degranulation, innate immune activation, and Th17-associated signalling networks centred on IL-17A and CXCL8. No proteins were significantly differentially expressed between PP and HPE lesions. PP and HPE showed overlapping interferon-associated chemokines CXCL10-11, consistent with a shared inflammatory module. Inflammatory protein levels decline with clinical improvement in longitudinal PP samples. Overall, tape strip-based targeted proteomics is a feasible approach for palmoplantar diseases, revealing a distinct inflammatory signature that differentiates PPP from PP and HPE, although discrimination between PP and HPE remains limited.