Solar Urticaria (SU) is a rare, chronic inducible urticaria characterised by an itching or burning erythemal flare with or without whealing, that can develop within minutes of exposure to ultraviolet radiation (UVR) and/or visible light. It is hypothesised that an unidentified endogenous photo-allergen may be the trigger, leading to IgE-mediated mast cell degranulation. However, the evolution of the response and mechanisms involved are not well understood. We undertook a UVR provocation study with transcriptome analysis to examine early events in SU pathophysiology. Patients with diagnosed SU (n=4) were provoked on photoprotected upper buttock skin with 10J/cm2 solar simulated UVR. Skin biopsies were taken 30min, 3h and 24h post UVR exposure and from adjacent unexposed skin. A comparator group of healthy volunteers (n=4) underwent the same UVR exposure and biopsy protocol. Skin samples were analysed by RNAseq and immunofluorescent staining. Transcriptomic analysis revealed activation of inflammation and DAMP signalling pathways in SU patients but not healthy controls across all time points. Upstream regulator analysis highlighted TNFα, Toll-like receptors, and several interleukins. Immunofluorescence showed that extracellular release of TNFα was significantly higher in skin of SU patients as early as 30 minutes post UVR, but not in healthy controls (P=0.01). Notably, causal analysis predicted down-regulation of the transcription factor DLX3 in unexposed skin of SU patients compared to that of healthy controls. Immunofluorescence staining showed observably lower levels of epidermal DLX3 in SU patients compared to healthy controls. Our data show SU to involve early activation of chemotactic and inflammatory pathways following a single UVR exposure which is not seen in healthy skin. Baseline differences in DLX3 production indicate possible disruption of skin homeostasis in SU patients. Further analysis of these pathways will aid understanding of the mechanisms underlying SU with the potential to identify new therapeutic targets.

ESDR521 - Deciphering Pathomechanisms in Solar Urticaria

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.