Greco C, Leclerc-Mercier S, Chaumo S, et al. - Researchers designed a case series, 3 people from 2 unrelated families who had TRPV3-mutation–associated palmoplantar keratoderma (PPK) were treated with erlotinib from May 5, 2018, through May 13, 2019, in order to investigate the possibility of blocking epidermal growth factor receptor (EGFR) transactivation with the inhibitor erlotinib hydrochloride to treat PPK in individuals with Olmsted syndrome due to TRPV3 mutations. Participants (3 individuals) had severe palmoplantar hyperkeratosis, unbearable pain with erythromelalgia, severe growth delay, anorexia, and insomnia, which had been growing since infancy in spite of numerous therapies. Due to hyperkeratosis, two individuals were limited to wheelchairs owing to intense pain and joint restrictions. They were unable to engage in social activities because they underwent depression. Finding suggests that when treated with erlotinib, improvement of PPK in people with Olmsted syndrome caused by TRPV3 mutations. Moreover, targeting EGFR transactivation with erlotinib therapy might result in clinical remission in an orphan disease that lacks an effective intervention.