A case of peeling skin syndrome type 1 with novel CDSN gene variation successfully treated with upadacitinib

Abstract Peeling skin syndrome type 1 (PSS1) is an autosomal recessive genodermatosis caused by the CDSN gene loss‐of‐function mutation and characterized by widespread superficial skin peeling and erythroderma with unbearable pruritus. Because of its ultra‐rarity and unclear mechanism, this rare disease has no established treatment regimen. Herein, we reported a Chinese woman who presented with congenital generalized pruritic erythroderma and exfoliation, notable for significantly elevated IgE levels. The whole exome sequencing identified an unpublished homozygous variant (c.295C>T, p.Gln99*) in the CDSN gene, confirming the diagnosis of PSS1. Immunohistochemistry analysis of the affected skin confirmed the lack of corneodesmosin expression, revealed the overexpression of T helper 2 (Th2)–related cytokines harboring interleukin (IL) 4 and IL‐13. After Janus kinase 1 (JAK1) inhibitor upadacitinib administration, both the patient's skin rashes and itching symptoms were significantly alleviated. Our work expanded the PSS1‐related CDSN gene mutation spectrums, substantiated the hypothesis regarding the overexpression of Th2‐related cytokines, and uncovered the important role of JAK1 underlying PSS1. JAK1 signaling may dominate the pathogenesis in PSS1 and represent a potential therapeutic target.