Exploring Pruritus in Bullous Pemphigoid; Analysis of Quality-of-Life Metrics and Potential Biological Mechanisms

Abstract

Bullous pemphigoid (BP) is a devastating autoimmune blistering disease with need for improved therapeutics. Limited data is available on the overall burden of pruritus and alterations over time, however treatment of itch specific pathways may provide novel therapeutics. In this paper, we analyzed the quality-of-life (QOL) impact particularly related to itch and determined corresponding changes in intraepidermal nerve fiber density (IENFD) and gene expression. 43 BP patients were followed prospectively on standard-of-care treatment and showed average BPDAI total activity score (TAS) decrease from 19.1 ± 19.2 to 8.2 ± 11.3 and improvement in QOL measures ABQoL, TABQoL and ItchyQoL. At baseline, IENFD in BP and Atopic Dermatitis (AD) patients were significantly lower than healthy controls (7.3 ± 1.5, 3.2 ± 2.0 and vs. 9.7 ± 5.4 fibers/mm, p=0.031) and increased from baseline to follow-up visit, (11.7 ± 0.4 and 5.8 ± 2.7) although only AD reached statistical significance (p=0.018). S100A8, S100A9, CCL17 and CCL18, genes were highly upregulated in the skin of BP patients compared to healthy controls. Our data provides evidence for improvements in itch-related QOL over time on standard of care therapies with unique alterations in inflammatory mediators related to early immune cell activation and recruitment.