A case of peeling skin syndrome type 1 with novel CDSN gene variation successfully treated with upadacitinib
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Published on: April 7, 2023
Yusha Chen1,2, Jia Geng3, Yue Xiao1,2
1Department of Dermatology, West China Hospital, Sichuan University, Chengdu, China.
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 The whole exome sequencing identified an unpublished homozygous variant (c.295C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.
Insights
Peeling Skin Syndrome type 1 (PSS1) is a rare genetic skin disorder. A novel CDSN gene mutation was identified, and JAK1 inhibitor therapy showed significant symptom relief, suggesting JAK1 as a potential treatment target.
Area of Science:
- Dermatology
- Genetics
- Immunology
Background:
- Peeling Skin Syndrome type 1 (PSS1) is a rare autosomal recessive genodermatosis.
- It stems from CDSN gene mutations, causing skin peeling, erythroderma, and intense itching.
- Current treatment options for PSS1 are limited due to its rarity and unclear mechanisms.
Purpose of the Study:
- To identify the genetic cause of PSS1 in a Chinese patient.
- To investigate the underlying molecular mechanisms, including cytokine expression.
- To evaluate the efficacy of JAK1 inhibitor therapy for PSS1.
Main Methods:
- Whole exome sequencing to identify CDSN gene variants.
- Immunohistochemistry to analyze corneodesmosin expression and Th2 cytokine levels.
- Clinical assessment of patient response to upadacitinib (JAK1 inhibitor).
Main Results:
- A novel homozygous variant (c.295C>T, p.Gln99*) in the CDSN gene was identified, confirming PSS1 diagnosis.
- Lack of corneodesmosin expression and overexpression of IL-4 and IL-13 were observed in affected skin.
- Upadacitinib treatment led to significant improvement in skin rashes and pruritus.
Conclusions:
- This study expands the known CDSN mutation spectrum for PSS1.
- It supports the role of Th2 cytokine overexpression in PSS1 pathogenesis.
- JAK1 signaling is implicated in PSS1, presenting upadacitinib as a potential therapeutic strategy.
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