Greco C, Leclerc-Mercier S, Chaumon S, et al. - This study was intended to explore the possibility of blocking epidermal growth factor receptor (EGFR) transactivation with the inhibitor erlotinib hydrochloride to treat PPK in patients with Olmsted syndrome due to TRPV3 mutations. Between May 5, 2018, and May 13, 2019, three individuals from 2 unrelated families who had TRPV3-mutation–associated PPK were treated with erlotinib. Assessment of palmoplantar keratoderma (PPK) progression, pain, and interventions for pain, as well as erlotinib dose adjustment based on treatment impact, plasma levels, and tolerance were the main outcomes and measures. It was noted that erlotinib improved PPK in individuals with Olmsted syndrome caused by TRPV3 mutations. The study found that targeting EGFR transactivation with erlotinib therapy may appear in clinical remission in an orphan disease that lacks an effective intervention.