Pityriasis rubra pilaris (PRP) represents a group of rare inflammatory skin disorders. Diagnosis is often challenging, its treatment is mainly empirical and suffers from the lack of controlled trials. PRP shares overlapping clinical and histological features with psoriasis, suggesting a common underlying pathophysiology. Based on this resemblance, a role of the IL23–TH17-axis in PRP was proposed, and several cases of successful treatment of PRP with psoriasis biologics were reported. However, efficacy remains variable and these therapeutic options lack a valid immunopathological rationale. Thus, a better understanding of PRP pathophysiology is needed to improve its diagnosis and management. To this end, we performed transcriptomic analyses of PRP lesional skin using NanoString technology. Results were compared to a large cohort of common inflammatory skin diseases. Molecular profiling revealed a PRP-specific inflammatory signature accurately discriminating PRP from other inflammatory skin disorders, including psoriasis. Ultimately, this signature could serve as a robust disease classifier for accurate diagnosis. Intriguingly, PRP did not demonstrate TH1-, TH2-, nor a typical TH17-related signature. In fact, top upregulated cytokines in PRP are expressed by lymphocytes, but are mainly produced by keratinocytes. Using single cell RNAseq and in situ gene expression analyses, keratinocytes were indeed identified as key cellular source of the PRP-signature cytokines. Our data suggest that PRP and psoriasis are driven by distinct immunopathogenic pathways. While psoriasis is a TH17-mediated disease, PRP is a rather T-cell independent disorder mediated primarily by keratinocytes. These results could explain variable response of PRP to IL17 blockage and should help guiding rational therapeutic choices.

ESDR411 - Keratinocytes drive a specific inflammatory gene signature in pityriasis rubra pilaris

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.