Composition and structure of stratum corneum intercellular lipids in patients with osimertinib-induced hand-foot syndrome

Purpose: Osimertinib (OSM), a third-generation epidermal growth factor receptor tyrosine kinase, causes skin disorders, such as hand-foot syndrome (HFS), which impairs skin barrier function. Stratum corneum (SC) lipids play an important role in skin barrier function. This study aimed to compare the SC lipid composition and structure of healthy participants with those of patients with OSM-induced HFS. Methods: Overall, 47 patients with non-small cell lung cancer were enrolled in this study. All patients received 80 mg/day OSM orally. SC samples were obtained from seven patients with OSM-induced HFS (OSC). SC lipid composition (ceramide [CER] and free fatty acids [FFAs]) and structure were analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and synchrotron X-ray diffraction, respectively. Results In healthy SC (HSC), the lipids formed two lamellar phases. Hexagonal and orthorhombic hydrocarbon chain packing was observed in the lateral lipid organization. However, in the OSC, these structures almost disappeared. UPLC-MS/MS analysis revealed that the composition of CER and FFA differed between CSC and HSC and that the carbon chain length of SC lipid components in CSCs was lower compared with that in HSCs. However, no significant differences were observed in the CER levels of the esterified ω-hydroxy fatty acid class, which is involved in the formation of long-period lamellar structures, between the two groups. Conclusion: OSM induces changes in SC lipid structure due to changes in SC lipid composition and decreased in carbon chain length in OSCs, resulting in impaired barrier function.