Zhang A, Duchatelet S, Lakdawala N, et al. - Because Olmsted syndrome is a rare and disabling genodermatosis for which no successful treatment is currently available experts, intend to assess the clinical response to the mammalian target of rapamycin (mTOR) inhibitor sirolimus and/or the epidermal growth factor receptor (EGFR) inhibitor erlotinib among people with Olmsted syndrome. They designed case series concentrated on 4 children with treatment-refractory Olmsted syndrome. These children received treatments (initiated in 2017 and 2018) at the outpatient dermatology clinic at the Children’s Hospital of Wisconsin in Milwaukee, Wisconsin; Children’s National Hospital in Washington, DC; and Hospital Infantil Pequeno Príncipe, Curitiba in Paraná, Brazil. In the epidermis, lesional skin immunostaining showed increased phosphorylated ribosomal protein S6 (RPS6) and phosphorylated EGFR staining and also revealed enhanced mTOR and EGFR signaling activation. It was found that in the pathophysiological process of Olmsted syndrome, the EGFR-mTOR cascade might be played a substantial role and serve as a major therapeutic target. Oral sirolimus and erlotinib for pediatric patients with Olmsted syndrome can be a promising, life-altering treatment.