The blood proteomic signature of prurigo nodularis (PN) reveals distinct inflammatory and neuropathic endotypes: a cluster analysis - Supplement

Background: Prurigo nodularis (PN) is an extremely pruritic, chronic inflammatory skin disease. Little is known about systemic inflammation in PN.

Objective: To characterize plasma inflammatory biomarkers in PN patients and investigate the presence of disease endotypes.

Methods: In this cross-sectional study, Olink proteomic analysis was performed on plasma samples from PN patients (n=29) and healthy controls (n=18).

Results: PN patients had increased levels of eight circulating biomarkers compared to controls, including tumor necrosis factor (TNF), C-X-C Motif Chemokine Ligand 9 (CXCL9), interleukin (IL)-12B, and TNF receptor superfamily member 9 (TNFRSF9) (p<0.05). Two PN clusters were identified in Cluster 1 (n=13) and Cluster 2 (n=16). Cluster 2 had higher levels of 25 inflammatory markers than cluster 1. Patients in Cluster 1 had a greater percentage of patients with a history of myelopathy and spinal disc disease compared to Cluster 2 (69% vs. 25%, p=0.03). Patients in Cluster 2 were more likely to have a history of atopy (38% in cluster 2 vs. 8% in cluster 1, p=0.09). The supplemental data also demonstrate Cluster 2 had higher levels of 30 inflammatory markers compared to healthy controls. A contingency table demonstrates higher atopy in Cluster 2 compared to Cluster 1.

Limitations: Small sample size precludes robust subgroup analyses.

Conclusion: This study provides evidence of neuroimmune-biased endotypes in PN and can aid clinicians in managing PN patients that are non-responsive to traditional therapies.