Department of Dermatology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
International Center for Wound Repair and Regeneration, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Clin Exp Dermatol. 2024 Jul 19;49(8):887-892. doi: 10.1093/ced/llae080.
Autosomal recessive congenital ichthyosis (ARCI) is a genetically heterogeneous disorder with aberrant skin scaling and increased transepidermal water loss (TEWL). Current treatments for ARCI are limited and suboptimal. We present the case of a 27-year-old man with ARCI resulting from a homozygous missense variant in TGM1. RNA-sequencing of lesional skin revealed aberrant Janus kinase-signal transducer and activator of transcription signalling, providing a rationale for innovative treatment with a Janus kinase inhibitor. We prescribed oral tofacitinib (11 mg daily) for 26 weeks. Rapid improvements in erythema and fissuring occurred within the first month. Sustained reductions in 5-D itch scale and Dermatology Life Quality Index scores were also observed. TEWL decreased for the first 10 weeks but increased thereafter. Tofacitinib downregulated inflammatory genes and pathways, while enhancing skin barrier markers. Moreover, transglutaminase 1 distribution was normalized although enzymatic activity remained deficient. This study suggests that oral tofacitinib may be a useful therapy to consider for patients with ARCI.
常染色体隐性先天性鱼鳞病（ARCI）是一种遗传异质性疾病，表现为皮肤脱屑和经皮水分丢失增加（TEWL）。目前针对 ARCI 的治疗方法有限且效果不佳。我们报告了一例由 TGM1 纯合错义变异引起的 ARCI 患者。皮损的 RNA 测序显示异常的 Janus 激酶信号转导和转录激活因子信号，为使用 Janus 激酶抑制剂进行创新性治疗提供了依据。我们为患者开了口服托法替布（每天 11mg），疗程 26 周。在第一个月内，红斑和皲裂迅速改善。5-D 瘙痒量表和皮肤病生活质量指数评分也持续降低。TEWL 在最初的 10 周内下降，但此后又增加。托法替布下调了炎症基因和通路，同时增强了皮肤屏障标志物。此外，尽管转谷氨酰胺酶 1 的活性仍然不足，但它的分布已恢复正常。这项研究表明，口服托法替布可能是治疗 ARCI 患者的一种有效方法。
