Interleukin-36 Is Highly Expressed in Skin Biopsies from Two Patients with Netherton Syndrome

Netherton syndrome (NS) is a rare autosomal recessive disorder that occurs due to a loss-of-function mutation in SPINK5; this loss results in significant inflammation, as well as perturbations of the skin barrier's integrity and functionality. While it is unclear which inflammatory pathways contribute to the development of NS, recent studies have demonstrated the expression of interleukin (IL)-17/IL-36, as well as several Th2 cytokines. Consequently, immunohistochemistry (IHC) with IL-36 may serve as a potential tool for aiding the histopathological diagnosis of this condition. In this case series, we present two cases of NS and capture their immunostaining pattern with IL-36. Both cases demonstrated robust expression of IL-36. This finding bolsters the hypothesis that NS is partially driven by Th17 activation and suggests the potential utility of IL-36 IHC as part of the workup for this rare and diagnostically elusive entity. LEKTI IHC was negative in one biopsy, revealing a limitation of this stain in diagnosing NS.