Differentiation and proteomic insights into psoriasis and TNFi-induced psoriatic dermatitis in pediatric patients

Summary: Psoriasiform dermatitis (PsoD) is a potential adverse effect of tumor necrosis factor inhibitor (TNFi) treatment. Differentiating TNFi-induced PsoD from plaque psoriasis (PsO) can be challenging in children. Tape strips were collected from lesional skin of pediatric patients with PsO (n=13) and TNFi-PsoD (n=11) (mean age 12.7 years; mean Physician Global Assessment scores 2.9 vs 2.7, respectively, p>0.05) and from age/sex-matched healthy control (hc) skin (n=20). Affected body surface area was greater in PsO (15%) vs. TNFi-PsoD (2%) and non-scalp body sites (TNFi-PsoD especially on retroauricular, face, and palm) and morphology (TNFi-PsoD less well circumscribed and crustier) differed. Olink proteomic analysis was performed on proteins extracted from tape strips and identified 362 distinct proteins. Principal Component Analysis (PCA) showed distinct separation between all three groups based on disease identities, unaffected by age, sex or race. Differential protein expression based on ANOVA testing showed enriched Th1 (CXCL9/10), Th17 (IL17A) and Th2 (IL4R) pathways, as well as chemokines supporting immune cell infiltration (CXCL8, CCL4) and VEGFA between PsO and TNFi-PsoD groups. Most interesting among 19 proteins differentially expressed in PsO vs. TNFi-PsoD were IL-17C (higher in PsO; adj p<0.001; major IL-17 produced by keratinocytes), and LSP1 (adj p=0.006; neutrophil infiltration), HCLS1 (adj p=0.016; involved in immune responses), and CD200R1 (adj p=0.03; regulates skin cell interactions with CD4+ T cells and expression of TNFa, interferons, and inducible nitric oxide) (TNFi-PsoD>PsO). These data suggest that a small panel of tape-stripped proteins can distinguish pediatric PsO vs TNFi PsoD and provide insight into these pediatric disorders. Bao Xin Liang¹, Mariana McCune¹, Andie Kwon¹, Sheshanna Phan¹, Ethan H. Yang¹, Lydia Rabbaa Khabbaz¹, Ziyou Ren¹, Jennifer B. Scott¹, Stephanie Rangel¹, Amy Paller¹ 1. Dermatology, Northwestern University Feinberg School of Medicine, Chicago, IL, United States. Clinical Research: Epidemiology and Observational Research