846 A new case series of olmsted syndrome subjects confirms EGFR activation and long term efficacity of oral erlotinib with acceptable tolerance

Olmsted syndrome (OS) is a rare, painful and severe form of palmoplantar keratoderma (PPK). It most often caused by dominant mutations in the transient receptor potential vanilloid-3 (TRPV3) gene, heat-sensitive ion channel that forms signaling complex with epidermal growth factor (EGFR). TRPV3 are thought to activate EGFR causing abnormal keratinocyte proliferation differentiation. We previously reported blocking oral Erlotinib resulted remarkable improvement 4 young patients. Here, we describe activation situ evaluate long-term efficacy tolerance 9 OS patients (3-to 58-year-old) up 39 months. Active homodimers were directly assessed proximity ligation assay revealed significant increase hyperkeratotic lesions. mTOR pathway transglutaminase-1 activity upregulated consistent activation. Treatment improved quality life Specifically, showed near complete resolution PPK, pain, pruritus, few side effects; 2 had comparable but poorer tolerance; 3 partial reduction pain good tolerance. Our results confirm reveal long term acceptable inter-individual differences