554 Cluster analysis of circulating plasma biomarkers in prurigo nodularis reveals a distinct systemic inflammatory signature in African Americans

Patients with prurigo nodularis (PN) suffer from intractable itch and dramatic reduction in quality of life. While there is significant clinical heterogeneity in the presentation of PN, disease endotypes remain unknown. We assayed circulating plasma cytokine concentrations in PN patients (n=20) along with matched healthy controls and utilized an unsupervised machine learning algorithm to identify disease endotypes. We found two distinct clusters of PN patients with non-inflammatory (Cluster 1) and inflammatory (Cluster 2) plasma profiles. Cluster 2 had more African-Americans (82%, n=9 vs. 33%, n=3; P=0.028), higher worst-itch numeric rating scale scores (9.5±0.9 vs. 8.3±1.2; P=0.036), and lower quality of life as reflected by higher Dermatology Life Quality Index scores (21.9±6.4 vs. 13.0±4.1; P=0.015). In addition, Cluster 1 had a higher rate of myelopathy (67%, n=6 vs. 18%, n=2; P=0.028). Compared to Cluster 1, Cluster 2 had higher levels of IL-1α, IL-4, IL-5, IL-6, IL-10, IL-17A, IL-22, IL-25, and IFN-α. With population-level analysis, African-American PN patients had higher erythrocyte sedimentation rate, C-reactive protein, ferritin, eosinophils, and lower transferrin than Caucasian PN patients. These findings indicate discrete clusters of PN patients with plasma biomarker profiles corresponding to distinct demographic and clinical characteristics, potentially allowing for precision medicine approaches to treat PN.