Pruritus (itch) is an important symptom in dystrophic epidermolysis bullosa (DEB). The causative mechanisms are unknown, and treatments are limited. In this study, we investigated DEB itch using multi-omic approaches. We recruited 15 subjects with the extremely itchy form of DEB, EB pruriginosa (DEB-P), and two matched control groups comprising 15 non-itchy DEB subjects (DEB-NP) and 15 healthy volunteers (HV). Blood and skin samples from lesional and non-lesional areas were collected. Blood proteomics and transcriptomics, and skin transcriptomics were compared between groups. One-way ANOVA analysis of the 3 groups identified 56 differentially abundant proteins in plasma (B-H p-value<0.1). Enrichment analysis showed 11 and 12 blood coagulation pathways were upregulated in DEB-P compared with DEB-NP and HV, respectively (B-H p-value<0.05). Differential expression analysis using DESeq2 revealed 2118 differentially expressed genes (DEGs, absolute log2 fold change>1, FDR<0.05) between lesional DEB-P and normal skin (including non-lesional DEB-P and HV samples). Ingenuity Pathway Analysis (IPA) indicated 37 significantly dysregulated pathways (absolute z-score>2, -log(B-H p-value)>1.3) in lesional DEB-P skin, including immune cell adhesion and diapedesis. Comparison between lesional DEB-P and DEB-NP (non-itchy, lesional) skin showed 2115 DEGs, with 10 significantly dysregulated pathways in lesional DEB-P skin, most notably CREB (cAMP response element-binding protein) signalling in neurons, eicosanoid signalling and cholesterol biosynthesis. Collectively, these data provide new insight into DEB itch pathobiology and identify potential targets germane to improving patient symptoms.

ESDR069 - Multi-omic analyses highlight key molecular pathways in dystrophic epidermolysis bullosa pruriginosa

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING