262 The Role of Cholesterol in Rare Inflammatory Skin Disease

Inflammatory linear verrucous epidermal naevus (ILVEN) is a rare congenital disease characterised by Blaschko-linear erythematous scaly skin. It highly pruritic, disfiguring, and notoriously treatment-resistant. The genetic basis heterogeneous: causes so far established are single case of GJA1- two CARD14- mosaicism. However, clinical overlap with the skin lesions CHILD syndrome led us to hypothesise that there may be common biological pathway abnormality in ILVEN centred on cholesterol metabolic pathways. Ten patients no other features (GJA1 CARD14 wildtype) ten healthy controls (excess normal from surgery) were recruited biopsied. Deep whole exome sequencing affected revealed had unsuspected (Congenital Hemidysplasia, Ichthyosiform Erythroderma Limb Defects) germline NSDHL variants. Keratinocytes cultured HPV immortalised, then using proliferation assays, Filipin III staining optimised 2-dimensional Gas-Chromatography mass spectrometry. Strikingly, mean total levels three sterol intermediates synthesis significantly reduced patient group compared controls. In parallel we observed significant hyper-proliferation keratinocytes at baseline controls, which was rescued addition isolation Simvastatin. Treatment clinic topical 2% + lovastatin effective both as previously shown, partial correction further without known disorder metabolism. These findings identify role for pathogenesis raise important questions about regulation inflammatory lipid